Metal complexes with bifunctional imidazolyl phosphines for catalytic organic transformations

UC San DiegoUC San Diego Electronic Theses and Dissertations

TitleMetal complexes with bifunctional imidazolyl phosphines for catalytic organic transformations : applications in homogeneous and polymer supported alkene isomerization , and hydrogen deuterium exchange

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AuthorErdogan, Gulin

Publication Date2012 Peer reviewed|Thesis/dissertation

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UNIVERSITY OF CALIFORNIA, SAN DIEGO SAN DIEGO STATE UNIVERSITY

Metal Complexes with Bifunctional Imidazolyl Phosphines for Catalytic Organic Transformations: Applications in Homogeneous and Polymer Supported Alkene

Isomerization , and Hydrogen Deuterium Exchange

A dissertation submitted in partial satisfaction of the

requirements for the degree Doctor of Philosophy in

Chemistry

by

Gulin Erdogan

Committee in charge:

University of California, San Diego

Professor Joshua S. Figueroa Professor William H. Gerwick Professor Charles L. Perrin

San Diego State University

Professor Douglas B. Grotjahn, Chair Professor B. Mikael Bergdahl Professor Terrence G. Frey

2012

Copyright

Gulin Erdogan , 2012

All rights reserved.

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The dissertation of Gulin Erdogan is approved, and it is acceptable in quality and form for publication on microfilm: _____________________________________________

_____________________________________________

_____________________________________________

_____________________________________________

_____________________________________________

_____________________________________________

Chair


San Diego State University

2012

iv

DEDICATION

To cheese, wine, and beer.

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TABLE OF CONTENTS

Signature Page ...................................................................................................................iii

Dedication .........................................................................................................................iv

Table of Contents ...............................................................................................................v

List of Tables ....................................................................................................................vi

List of Figures.....................................................................................................................x

Acknowledgements ..........................................................................................................xv

Vita, Publications and Fields of Study ………………………………………………....xx

Abstract .........................................................................................................................xxiv

Chapter 1 Introduction – Bifunctional Catalysis …….......................................................1

Chapter 2 Development of New Bifunctional Cyclopentadienyl Ruthenium Imidazolyl

Phosphine Complexes for Controlled Alkene Isomerization ............................................19

Chapter 3 Polymer Supported Alkene Isomerization…………......................................120

Chapter 4 Mild and Selective Hydrogen / Deuterium Exchange at Allylic Positions of

Olefins .............................................................................................................................191

Chapter 5 Conclusions and Future Directions.................................................................232

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LIST OF TABLES

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Table 2.1. Isomerization of allylic alcohols by 2.4 and 2.5 at 100 oC in 1,4-dioxane with 10 mol% Et3NHPF6................................................................................25

Table 2.2. Isomerization of allylic alcohols by 2.4 and 2.5 at 57 oC in chloroform-d....................................................................................................................................26

Table 2.3. Scope of alkene isomerization catalyst 2.10a..........................................................30 Table 2.4. Important bond lengths and angles for 2.10, 2.26, and 2.27...................................38 Table 2.5. Calculated product distribution of heptenes ...........................................................41 Table 2.6. Collective isomerization data of 1-heptene, and equilibrium

composition predicted from Table 2.5 .........................................................................44 Table 2.7. Crystal data and structure refinement for 2.26 .......................................................52

Table 2.8. Atomic coordinates (x 104) and equivalent isotropic displacement parameters (Å2x 103) for 2.26. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.......................................................................................53

Table 2.9. Anisotropic displacement parameters (Å2x 103) for 2.26. The anisotropic displacement factor exponent takes the form: -2p2[ h2 a*2U11 + ... + 2 h k a* b* U12] ................................................................................................57

Table 2.10. Bond lengths and angles for 2.26..........................................................................61 Table 2.11. Crystal data and structure refinement for 2.27 .....................................................71

Table 2.12. Atomic coordinates (x 104) and equivalent isotropic displacement parameters (Å2x 103) for 2.27. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.......................................................................................72

Table 2.13. Anisotropic displacement parameters (Å2x 103) for 2.27. The anisotropic displacement factor exponent takes the form: -2π2[ h2 a*2U11 + ... + 2 h k a* b* U12 ] ................................................................................78

Table 2.14. Bond lengths and angles for 2.27..........................................................................83 Table 2.15. 1-heptene Isomerization with 2 mol % 2.10 in NMR probe...............................105 Table 2.16. 1-heptene Isomerization with 2 mol % 2.19 at RT.............................................105 Table 2.17. 1-heptene Isomerization with 2 mol % 2.19 in NMR probe...............................106

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Table 2.18. 1-heptene Isomerization with 2 mol % 2.20 at RT.............................................106 Table 2.19. 1-heptene isomerization with 2 mol % 2.20 at 70 oC .........................................107 Table 2.20. 1-heptene isomerization with 2 mol % 2.21 at 70 oC .........................................107 Table 2.21. 1-heptene isomerization with 2 mol % 2.22 at RT .............................................108 Table 2.22. 1-heptene isomerization with 2 mol % 2.23 at RT ge715 ..................................108 Table 2.23. 1-heptene isomerization with 2 mol % 2.23 at 70 oC .........................................109 Table 2.24. 1-heptene isomerization with 2 mol % 2.23 at 70 oC .........................................109 Table 2.25. 1-hexene isomerization with 2 mol % 2.20 at RT and 70 oC..............................110 Table 2.26. 1-decene isomerization with 2 mol % 2.20 at 70 oC...........................................110 Table 2.27. 1-hexene isomerization with 2 mol % 2.23 at RT ..............................................111 Table 3.1. Supports for immobilization .................................................................................122 Table 3.2. Scope of polymer-supported Felkin’s iridium catalyst.........................................129 Table 3.3. Substrate scope of PS-1 and PSL-1......................................................................134 Table 3.4. Recycling experiments performed with PS-1 and amount of metal

leaching ......................................................................................................................138 Table 3.5. Reaction conditions for optimal 1-(4-bromobenzyl)-4-(tBu)-imidazole

synthesis.....................................................................................................................143 Table 3.6. Isomerization of 4-allylanisole with PS-1 ............................................................158 Table 3.7. Isomerization of 4-allylanisole with PSL-1..........................................................159 Table 3.8. Isomerization of 4-allylanisole with 2.10 .............................................................159 Table 3.9. Isomerization of allyloxy(tert-butyl)dimethylsilane with PS-1............................160 Table 3.10. Isomerization of allyloxyallyloxy(tert-butyl)dimethylsilane with PSL-

1..................................................................................................................................161 Table 3.11. Isomerization of allyloxy(tert-butyl)dimethylsilane with 2.10...........................161 Table 3.12. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 5

mol% PS-1 .................................................................................................................162 Table 3.13. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 5

mol% PSL-1 ..............................................................................................................163 Table 3.14. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 2

mol% PS-1 .................................................................................................................163 Table 3.15. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 2

mol% PSL-1 ..............................................................................................................164 Table 3.16. Isomerization of methylenecyclohexane with PS-1 ...........................................165 Table 3.17. Isomerization of methylenecyclohexane with PSL-1.........................................165

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Table 3.18. Isomerization of methylenecyclohexane with 2.10 ............................................166 Table 3.19. Isomerization of allyl ether with PS-1 ................................................................167 Table 3.20. Isomerization of allyl ether with PSL-1 .............................................................167 Table 3.21. Isomerization of 4-penten-2-ol with PS-1 ..........................................................168 Table 3.22. Isomerization of 4-penten-2-ol with PSL-1........................................................168 Table 3.23. Isomerization of 2-allylcyclohexanone with PS-1..............................................169 Table 3.24. Isomerization of 2-allylcyclohexanone with PSL-1 ...........................................170 Table 3.25. Isomerization of 2-allylcyclohexanone with 2.10...............................................170 Table 3.26. Isomerization of eugenol with PS-1 ...................................................................171 Table 3.27. Isomerization of eugenol with PSL-1.................................................................172 Table 3.28. Isomerization of eugenol with 2.10 ....................................................................172 Table 3.29. Neat isomerization of 4-penten-2-ol with PS-1 ..................................................173 Table 3.30. Neat isomerization of 4-penten-2-ol with PSL-1 ...............................................174 Table 3.31. Neat isomerization of eugenol with PS-1 ...........................................................174 Table 3.32. Neat isomerization of eugenol with PSL-1 ........................................................175 Table 3.33. Neat isomerization of 2-allylcyclohexanone with PS-1 .....................................176 Table 3.34. Neat isomerization of 2-allylcyclohexanone with PSL-1...................................176 Table 3.35. Amount of starting material and internal standard used for recycling

experiments ................................................................................................................184 Table 3.36. Isomerization activity from recycling experiments with PS-1 and

PSL-1 .........................................................................................................................185 Table 3.37. Ruthenium leaching from recycling experiments performed with PS-1

and PSL-1 ..................................................................................................................186 Table 3.38. Leaching in mass ruthenium per cycle with PS-1 ..............................................186 Table 4.1. % Hydrogen left at indicated positions of propene after specified time...............209 Table 4.2. % Hydrogen atoms present at specified positions in reaction of (Z)-2-

butene in presence of water........................................................................................211 Table 4.3. % Hydrogen atoms present at specified positions in reaction of (Z)-2-

butene in presence of deuterium oxide ......................................................................213 Table 4.4. % Hydrogen atoms present at specified positions in reaction of (E)-2-

butene in presence of water........................................................................................214 Table 4.5. % Hydrogen atoms present at specified positions in reaction of (E)-2-

butene in presence of deuterium oxide ......................................................................216

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Table 4.6. % Hydrogen atoms present in 2-pentene with deuterium oxide at room temperature ................................................................................................................217

Table 4.7. % Hydrogen atoms present in 2-pentene with deuterium oxide at 70 oC .............218 Table 4.8. % Hydrogen left at indicated positions of (E)-anethole after specified

time at room temperature ...........................................................................................219 Table 4.9. % Hydrogen left at indicated positions of (E)-anethole after specified

time at 70 oC...............................................................................................................219 Table 4.10. % Hydrogen left at indicated positions of (E)-anethole after specified

time at room temperature under biphasic setting.......................................................221 Table 4.11. % Hydrogen left at indicated positions of (E)-anethole after specified

time at 70 oC under biphasic setting ..........................................................................222 Table 4.12. % Hydrogen left at the specified positions of (E)-propenyl ether with

deuterium oxide at room temperature ........................................................................223 Table 4.13. % Hydrogen left at the specified positions of 4-methyl-2-pentene with

deuterium oxide at room temperature ........................................................................224 Table 4.14. % Hydrogen left at the specified positions of (+)-limonene with

deuterium oxide at 70 oC............................................................................................225 Table 4.15. % Hydrogen left at the specified positions of (+)-valencene with

deuterium oxide at 70 oC............................................................................................227 Table 5.1. Results of initial arylamination screening with pre-formed complexes ...............237

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LIST OF FIGURES

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Figure 1.1 Reaction catalyzed by LADH, oxidation of ethanol ................................................3 Figure 1.2. Alcohol dehydrogenase mechanism of action in active site....................................4 Figure 1.3. Oxidation of D-galactose to D-galacto-hexodialdose .............................................5 Figure 1.4. Organization of the galactose oxidase active site....................................................5 Figure 1.5. Reaction mechanism proposed for galactose oxidase .............................................6 Figure 1.6. Shvo’s catalyst and proposed bifunctional mechanism...........................................7 Figure 1.7. Noyori’s catalyst and proposed bifunctional mechanism........................................8 Figure 1.8. Dearomatization and aromatization of Milstein’s complexes .................................9 Figure 1.9. Representative bifunctional complexes developed in the Grotjahn lab ................10 Figure 1.10. Anti-Markovnikov alkyne hydration ...................................................................11 Figure 1.11. Alkyne hydrogen bonding in intermediates related to anti-

Markovnikov hydration ...............................................................................................12 Figure 1.12. Importance of pendant base substituents on structure and reactivity ..................13 Figure 1.13. Hydration equilibrium of CpRu imidazolyl comlexes 1.12 and 1.13..................13 Figure 1.14. Comparison of pyridine and imidazole pendant base effect on chelate

opening.........................................................................................................................14 Figure 1.15. Homogenous phase and polymer-supported alkene isomerization

catalyst .........................................................................................................................15 Figure 2.1. Selected alkene isomerizations involved in industrial processes ..........................21 Figure 2.2. Isomerization by Wilkinson’s catalyst ..................................................................22 Figure 2.3. Isomerization of allyl groups by metathesis catalyst 2.2.......................................23 Figure 2.3. Trost’s ruthenium complexes for allylic alcohol isomerization ............................24 Figure 2.4. Improved cyclopentadienyl ruthenium complexes for allylic alcohol

isomerization by Slugovc.............................................................................................26 Figure 2.5. CpRu precursor, pyridylphosphines and imidazolylphosphines used

for catalytic alkene isomerization screening................................................................28 Figure 2.6. Organic substrates used in catalytic alkene isomerization screening....................29 Figure 2.7. Alkene isomerization catalyst developed in Grotjahn research group ..................29

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Figure 2.8. Catalytic cycle for alkene insertion mechanism of isomerization.........................31 Figure 2.9. Catalytic cycle for allyl mechanism of alkene isomerization................................32 Figure 2.10 Proposed mechanism of alkene isomerization with 2.10 .....................................33 Figure 2.11. Proposed mechanism by Tao et al. ......................................................................34 Figure 2.12. Computational model of propene (shown with yellow colored

carbons) formed after loss of CH3CN from alkene isomerization catalyst 2.10...............................................................................................................................35

Figure 2.13. Sites for tuning of imidazolylphosphine ligands and catalysts ...........................36 Figure 2.14. Alkene isomerization catalyst and its more sterically hindered

analogues......................................................................................................................37 Figure 2.15. X-ray crystal structure of 2.26, hydrogens and counter anion hidden

for clarity......................................................................................................................39 Figure 2.16. X-ray crystal structure of 2.27, hydrogens and counter anion hidden

for clarity......................................................................................................................40 Figure 2.17. Heptene isomers with CH3 or CH2 groups used for NMR integrations

highlighted ...................................................................................................................43 Figure 2.18. Synthesis of 4-(tert-Butyl)-2-(di-iso-propylphosphino)-1-methyl-1H-

imidazole......................................................................................................................48 Figure 2.19. Synthesis of 4-(tert-Butyl)-2-(di-cyclohexylphosphino)-1-methyl-

1H-imidazole................................................................................................................49 Figure 2.20. Complexation of 2.25 to give 2.19 ......................................................................50 Figure 2.21. Anion exchange of 2.19.......................................................................................51 Figure 2.22. Synthesis of 2.20 .................................................................................................69 Figure 2.23. Anion exchange of 2.20.......................................................................................70 Figure 2.24. Synthesis of di-1-adamantylphosphinic chloride ................................................96 Figure 2.25. Synthesis of di-1-adamantylphosphine................................................................97 Figure 2.26. Synthesis of di-1-adamantylchlorophosphine .....................................................97 Figure 2.27. Synthesis of 4-(tert-butyl)-2-(di-1-adamatylphosphino)-1-methyl-1H-

imidazole......................................................................................................................98 Figure 2.28. Synthesis of 2.21 .................................................................................................99 Figure 2.29. Synthesis of 4-(1-adamantyl)-2-(di-iso-propylphosphino)-1-methyl-

1H-imidazole..............................................................................................................100 Figure 2.30. Complexation of 2.32 to give 2.22 ....................................................................101 Figure 2.31. Synthesis of 4-(1-adamantyl)-2-(di-tert-butylphosphino)-1-methyl-

1H-imidazole..............................................................................................................102

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Figure 2.32. Complexation of 2.33 to give 2.23 ....................................................................103 Figure 3.1. Immobilization of (E)-4-hydroxyproline.............................................................124 Figure 3.2. Reactions catalyzed by polystyrene immobilized (E)-4-hydroxyprline.

(a) Diasteroselective direct aldol reactions, (b) Enantioselective alpha-aminoxylation of ketones, (c) Enantioselective Mannich reactions ..........................125

Figure 3.3. PS-DES synthesis from Merrifield resin.............................................................125 Figure 3.4. Polymer-supported 2nd generation Hoveyda-Grubbs metathesis

catalyst .......................................................................................................................126 Figure 3.5. Polymer-supported Felkin’s iridium catalyst ......................................................128 Figure 3.6. Synthesis of polymer-supported alkene isomerization catalyst PS-1..................131 Figure 3.7. Synthesis of polymer-supported alkene isomerization catalyst PSL-1 ...............132 Figure 3.8. Isomerizations with PS-1 and PSL-1 under neat conditions...............................136 Figure 3.9. Sequential polymer-supported alkene isomerization and silica-

supported metathesis..................................................................................................137 Figure 3.10. Examples of soluble polymers...........................................................................140 Figure 3.11. Borylation of sPS with Ir-catalyzed C-H activation..........................................141 Figure 3.12. Facile functionalization of sPS-B(pin) .............................................................142 Figure 3.13. Benzyl spacer installment on 4-(tBu)-imidazole...............................................143 Figure 3.14. Synthesis of sPS-B(pin) and 1H NMR signals used to calculate %

incorporation ..............................................................................................................144 Figure 3.15. Functionalization of sPS-B(pin) .......................................................................145 Figure 3.16. Synthesis of sPS-1 .............................................................................................146 Figure 3.17. Synthesis of polystyrene-supported 4-tert-butyl-1-1H-imidazole.....................147 Figure 3.18. Synthesis of 4-tert-butyl-2-(diisopropylphosphino)-1H-imidazole ..................148 Figure 3.19. Synthesis of PS-1 ..............................................................................................149 Figure 3.20. 31P NMR spectrum of PS-2 (left) and PS-1 (right) ...........................................150 Figure 3.21. Synthesis of 2-(3-bromopropoxy)tetrahydro-2H-pyran ....................................151 Figure 3.22. Synthesis of 4-tert-butyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-

1H-imidazole..............................................................................................................152 Figure 3.23. 3-(4-tert-butyl-1H-imidazol-1-yl)propan-1-ol ..................................................153 Figure 3.24. Polystyrene-supprted 4-tert-butyl-1H-imidazol-1-yl group with linker............154 Figure 3.25. Polystyrene-supported 4-tert-butyl-2-(diisopropylphosphino-1H-

imidazole....................................................................................................................155 Figure 3.26. Synthesis of PSL-1............................................................................................156

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Figure 3.27. Isomerization of 4-allylanisole ..........................................................................158 Figure 3.28. Isomerization of allyloxy(tert-butyl)dimethylsilane .........................................159 Figure 3.29. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane ..............................161 Figure 3.30. Isomerization of methylenecyclohexane ...........................................................164 Figure 3.31. Isomerization of allyl ether................................................................................166 Figure 3.32. Isomerization of 4-penten-2-ol ..........................................................................167 Figure 3.33. Isomerization of 2-allylcyclohexanone .............................................................168 Figure 3.34. Isomerization of Eugenol ..................................................................................171 Figure 3.35. Sequential isomerization and metathesis of 4-allylanisole................................177 Figure 3.36. Sequential isomerization and metathesis of eugenol.........................................179 Figure 3.37. Sequential isomerization and metathesis of protected eugenol, (4-

allyl-2-methylphenoxy)(tert-butyl)dimethylsilane ....................................................181 Figure 4.1. H/D exchange of aromatic and aliphatic C-H bonds reported by

Bergman and coworkers ............................................................................................193 Figure 4.2. Deuteration of cyclooctene under hydrothermal conditions by

Matsubara and coworkers ..........................................................................................194 Figure 4.3. Deuteration of cyclohexene using microwave irradiation...................................195 Figure 4.4. H/D exchange reported by Brookhart and coworkers .........................................195 Figure 4.5. Scope of H/D exchange with [(dtbpp)Ir(H)(NH2)] .............................................197 Figure 4.6. Proposed mechanism of isomerization and deuteration by 2.10 .........................201 Figure 4.7. Isomerization of linear olefins.............................................................................202 Figure 4.8. (left) 1H NMR spectrum of 2-butene in presence of water. Geometrical

isomerization to a mixture of (E)- (major) and (Z)- (minor) 2-butenes in acetone-d6; (right) 1H NMR spectrum of 2-butene in presence of deuterium oxide. Conclusion: Deuteration is much more rapid than geometrical isomerization..........................................................................................203

Figure 4.9. Isomerization and selective deuteration of branched olefins ..............................204 Figure 4.10. Comparison progression of isomerization and H/D exchange of 4-

allylanisole in homogeneous and biphasic settings over time ...................................205 Figure 4.11. Deuteration of propene ......................................................................................209 Figure 4.12. 1H NMR Spectrum of (E)-2-butene in acetone-d6 (upper); (E)-

(major) and (Z)- (minor) 2-butenes in acetone-d6......................................................210 Figure 4.13. Control experiment with (Z)-2-butene in presence of water .............................211 Figure 4.14. Control experiment with (Z)-2-butene in presence of deuterium oxide ............212

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Figure 4.15. Control experiment with (E)-2-butene in presence of water .............................214 Figure 4.16. Deuteration of (E)-2-butene ..............................................................................215 Figure. 4.17. Isomerization and deuteration of 1-pentene .....................................................216 Figure 4.18. Isomerization and deuteration of 4-allylanisole ................................................218 Figure 4.19. Isomerization and deuteration of allyl ether......................................................222 Figure 4.20. Isomerization and deuteration of 4-methyl-1-pentene ......................................223 Figure 4.20. Selective deuteration of (+)-limonene ...............................................................224 Figure 4.21. 1H NMR Spectrum of (+)-limonene methyl peak 2 ..........................................226 Figure 4.22. Selective deuteration of (+)-valencene..............................................................226 Figure 5.1. Pharmaceutical applications of cross-coupling reactions....................................234 Figure 5.2. Representative ligands used for cross-coupling reactions...................................235 Figure 5.3. (η3-Allyl)palladium chloride complexes prepared by Reji Nair .........................236 Figure 5. 4. Screening reaction and conditions for arylamination.........................................237 Figure 5.5. In situ arylamination screening ligands and palladium precursors .....................238

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ACKNOWLEDGEMENTS

I have to admit my years in graduate school have been better than I hoped for.

First and foremost I’d like to thank Dr. Grotjahn for his endless patience, his support and

his passion for sharing chemistry. He has been more than an advisor and he is a life-long

mentor. Joining his group has been the decision that has definitely moved my life in the

direction for the better and I am truly grateful for his guidance.

More than anything, my group have been the source of fun through endless days

and nights of chemistry. I confess, I think sometimes we had more fun in the lab than

anywhere else we could have been. We even wondered what’s wrong with us, 10:30 pm

–still working in lab- on a St. Patrick’s night. I had the pleasure to work with many great

chemists. Dr. Valentin Miranda, I’ve been secretly envious of the number of experiments

you can get done. Dr. Sara Cortes-Llamas, the time you spent in Grotjahn lab during your

Fulbright Scholarship will always be remembered by the one liner “I love beer”, while

caressing a bottle of Sam Adams. Jeff Gustafson, you are brilliant, wish had more time

working with you. Jessica Lamonte is the person who cracked my shell to expose

everybody to my goofiness; she is the one to blame. Now she is known as Jessica Martin,

happily married to Kenny Martin; the man who gives the best hugs ever. It has pained me

that you guys moved to Tennessee. But no matter what the geographical constraints are, I

am grateful to be in your lives, I pray your friendship will always be by my side. Derek

Brown, you are the one person I can count on for anything and not think twice. Thank

you for being my rock and my sounding board. Hi, Hai! I know you hate it but I can’t

xvi

help it. My source of local dining tips, thank you for making me look cool when I had a

date. Derek and Hai, can’t express how much I admire your work ethic, dedication and

sense of responsibility. For all of us that worked with you during your years in lab, thank

you for keeping the glovebox on constant resuscitation, for making chemistry possible

and reliable. You were integral members of the Grotjahn group; he will be lucky to have

more people like you to work for him. Dr. Reji Nair, high five, buddy! No more is

needed. Andrea Rodriguez, one day you will save the world. Caline Abadjian, unicorn is

a legendary animal from European folklore, Cherrielee, Forsythia, Baby Fifi, Star Swirl,

Twist and Rarity are among the many unicorns of my little pony. How about that for

random facts, but I bet you already knew. You are my favorite person to spend

Valentine’s, next time we should just go watch PBR in real life. Miss Caseypants, can

you believe? You are the most unexpected friend of mine, wouldn’t have thought of it in

a million years that you would be one of the few people would end up knowing me so

well. I admire your joy for life and your pure excitement about trivial things in life. You

helped me appreciate small moments, hope your enthusiasm never changes, but I can’t

wait to see who you’ll be when you grow up! Thank you for getting me through the day,

for being the person who has my back. We have come so far. Your friendship is

invaluable and what has made this experience even better is how we work well together;

sharing ideas and information. Casey Larsen, I am so proud of you. Dave Marelius,

Jayneil Kamdar, Evan Darrow, thank you for making this year fun. All the rest of

Grotjahn Group members I had the chance to work with; Farhana Barmare, Zephen

Specht, Adria Lombardo, David Catrone, Erik Paulson, Lily Cao, Maulen Utiliyev,

Ariana Perez, Khoi Le, Abhi Sharma, Swetha Neravetla, Ruth Mendez, Ian Neel, Jeff

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Rafalski, Christoff van Niekerk, Paul Lee, Marly De Gracia, Christie Shulte, Xi Zeng,

Elijah Kragulj, Joanna Cuevas, Alice Lu, Meng Zhou. It has been fun!

The contents of Chapter 2 are similar to the material published in the following

papers: Grotjahn, Douglas B.; Larsen, Casey; Erdogan, Gulin; Gustafson, Jeffrey;

Sharma, Abhinandini; Nair, Reji. “Bifunctional catalysis of alkene isomerization and its

applications” Chemical Industries (Boca Raton, FL, United States) 2009, 123, 379-387.

Grotjahn, Douglas B; Larsen, Casey, R; Gustafson, Jeffery, L; Nair, Reji; Sharma,

Abhinandini. “Extensive isomerization of alkenes using a bifunctional catalyst: an alkene

zipper”. Journal of the American Chemical Society 2007, 129, 9592-9593. The

dissertation author was the primary researcher for the data presented and co-author on the

papers included. The co-authors listed in these publications also participated in the

research.

Chapter 3, in part is currently being prepared for submission for publication of the

material. Erdogan, Gulin; Grotjahn, Douglas B. “Polystyrene-Supported

Imidazolylphosphine Ligands and Cyclopentadienylruthenium Complexes for Highly

Selective Alkene Isomerization, Facile Product Purification, and Sequential Isomerization

/ Metathesis” The dissertation author was the primary researcher for the data presented.

Chapter 4 contains material are similar to the material published in the following

papers: Erdogan, Gulin; Grotjahn, Douglas B. “Catalysis of Selective

Hydrogen/Deuterium Exchange at Allylic Positions Using Deuterium Oxide” Topics in

Catalysis 2010, 53, 1055, Erdogan, Gulin; Grotjahn, Douglas B. “Mild and Selective

Deuteration and Isomerization of Alkenes by a Bifunctional Catalyst and Deuterium

Oxide” J. Am. Chem. Soc., 2009, 131, 30, 10354, and Grotjahn, Douglas B; Larsen,

xviii

Casey R.; Erdogan, Gulin; Gustafson, Jeffery L.; Nair, Reji; Sharma, Abhinandini

“Bifunctional Catalysis of Alkene Isomerization and Its Applications”, Catalysis of

Organic Reactions 2009, 123, 379. The dissertation author was the primary researcher for

the data presented.


material. Nair, Reji; Erdogan, Gulin; van Niekerk, Christoffel, Golen, James; Rheingold,

Arnold; Grotjahn, Douglas. The dissertation author was the primary researcher for the

data presented.

Cheryl and all the Severtsons; Lys, Anne, Maren; Todd Chamoy and the little

ones; Navah and Ilan. I am truly blessed to be welcomed in your family. Cheryl, you

have given me a sense of stability and belonging, made your home, my home. All of you

supported me through all these years and encouraged me on the days that you didn’t even

know how low I felt. I hope to make it Thursday night family dinner for years to come.

Isabelle and Andrew Lerario, and James Caldwell my very first friends in San

Diego! We had great time hiking, camping and all the trips we took looking for the trestle

in the middle of nowhere. James, thank you for helping me get my first car and all the

help to navigate through life in the United States. Isabelle and Andrew thank you for

having me crash on your couch numerous times and making me always feel welcome and

at home. I am looking forward to many more days to spend together in happy San Diego,

finally enjoying the sunshine to the last drip!

Finally, I’d like to thank all my family for their confidence and trust in me. For

letting me explore and supporting my decisions without doubt and quandary. My sister

Mine, thank you for all the wonderful trips around the world and keeping me connected

xix

to 41o N, 29o E. My sister Sema and cousin Senem, thank you for welcoming me home

every time I visit.

xx

CURRICULUM VITA

2005 B.S., Chemistry

Bogazici University, Istanbul, Turkey

2011 M.A., Chemistry

San Diego State University, San Diego, CA,

2012 Ph.D., Chemistry


PUBLICATIONS

Erdogan, Gulin; Grotjahn, Douglas B. “Catalysis of Selective Hydrogen/Deuterium

Exchange at Allylic Positions Using Deuterium Oxide” Topics in Catalysis 2010, 53,

1055.

Erdogan, Gulin; Grotjahn, Douglas B. “Mild and Selective Deuteration and Isomerization

of Alkenes by a Bifunctional Catalyst and Deuterium Oxide” J. Am. Chem. Soc., 2009,

131, 30, 10354.

Grotjahn, Douglas B; Larsen, Casey R.; Erdogan, Gulin; Gustafson, Jeffery L.; Nair,

Reji; Sharma, Abhinandini “Bifunctional Catalysis of Alkene Isomerization and Its

Applications”, Catalysis of Organic Reactions 2009, 123, 379.

Grotjahn Douglas B; Miranda-Soto Valentin; Kragulj Elijah J; Lev Daniel A; Erdogan

Gulin; Zeng Xi; Cooksy Andrew L., “Hydrogen-Bond Acceptance of Bifunctional

xxi

Ligands in an Alkyne-Metal pi Complex” Journal of the American Chemical Society

2008, 130(1), 20.

Ata Akın, Uzay E. Emir, Didem Bilensoy, Gulin Erdogan, Selcuk Candansyar,

Hayrunnisa Bolay, “fNIRS measurements in migraine”, Proc. SPIE, Photonics West

2005, 5693, 417.

ORAL PRESENTATIONS

Erdogan, Gulin; Grotjahn, Douglas B. “Bifunctional Complexes for Alkene Isomerization

and Hydrogen-Deuterium Exchange” 243rd American Chemical Society National

Meeting & Exposition, Anaheim, CA, USA, March 2012.

Erdogan, Gulin; Grotjahn, Douglas B. “Development of Bifunctional Phosphines and

Their Metal Complexes: Applications in Alkene Isomerization, Hydrogen-Deuterium

Exchange and Polymer-Immobilization” 5th Annual San Diego State University Student

Seminar Symposium, San Diego, CA, USA, March 2012.

Erdogan, Gulin; Grotjahn, Douglas B. “Development of Bifunctional Phosphines and

Their Metal Complexes: Applications in Hydrogen-Deuterium Exchange and Alkene

Isomerization“ Bogazici University Chemistry Department Seminars, Istanbul, Turkey,

January 2012.

Erdogan, Gulin; Grotjahn, Douglas B. "Bifunctional Catalysis of Alkene Isomerization /

Deuteration" 17th International Symposium on Olefin Metathesis and Related Chemistry

(ISOM XVII), Pasadena, CA, USA, August 2008.

xxii

POSTER PRESENTATIONS

Erdogan, Gulin; Grotjahn, Douglas B. "Polystyrene Based Bifunctional Ligands and

Their Applications in Catalytic Alkene Isomerization" Organometallic Chemistry Gordon

Research Seminar and Organometallic Chemistry Gordon Research Conference, Salve

Regina University, Newport, RI, USA, July 2011.

Erdogan, Gulin; Grotjahn, Douglas B. “Synthesis of Syndiotactic Polystyrene Based

Bifunctional Ligands and Their Applications in Catalysis” 241st American Chemical

Society National Meeting & Exposition, Anaheim, CA, USA, March 2011.

Erdogan, Gulin; Grotjahn, Douglas B. “Bifunctional alkene isomerization catalysts on

polymer support “ 239th American Chemical Society National Meeting & Exposition, San

Francisco, CA, USA, March 2010.

Erdogan, Gulin; Grotjahn, Douglas B. “Catalysis of Selective Hydrogen/Deuterium

Exchange at Allylic Positions Using Deuterium Oxide “ 23rd Organic Reactions Catalysis

Society Conference, Monterey, CA, USA, March 2010.

Erdogan, Gulin; Grotjahn, Douglas B. “Polymer Supported Alkene Isomerization

Catalysts ” 237th American Chemical Society National Meeting & Exposition, Salt Lake

City, UT, USA, 2009.

Erdogan, Gulin; Grotjahn, Douglas B. “Bifunctional Catalysis of Alkene Isomerization /

Deuteration" 17th International Symposium on Olefin Metathesis and Related Chemistry

(ISOM XVII), Pasadena, CA, USA, August 2008.

Erdogan, Gulin; Grotjahn, Douglas B. “Progress in: Bifunctional Catalysis of Alkene

Isomerization / Deuteration” 41st Annual Western Regional Meeting of the American

Chemical Society, San Diego, CA, USA, November 2007.

xxiii

Erdogan, Gulin; Grotjahn, Douglas B. “ Alkene Isomerization and Deuteration” VI

Simposio Internacional: Investigación Química EN LA Frontera Tijuana, B. C. México,

2006.

Erdogan, Gulin; Grotjahn, Douglas B. “ Alkene Isomerization and Deuteration” 232nd

American Chemical Society National Meeting & Exposition San Francisco, CA USA,

2006.

AWARDS

Inamori Fellowship 2011-2012.

Center for Enabling New Technologies Through Catalysis (CENTC) Summer School

Attendance, 2010.

International Precious Metals Institute (IPMI) Outstanding Student Award, 2010.

North American Catalysis Society (NACS) Student Travel Award for Organic Reactions

Catalysis Society (ORCS) Conference Participation, 2010.

MAJOR FIELDS OF STUDY

Major Field: Chemistry (Organic and Inorganic)

Studies in Synthesis and Organometallic Catalysis.

Professor Douglas B. Grotjahn

xxiv

ABSTRACT OF THE DISSERTATION

Metal Complexes with Bifunctional Imidazolyl Phosphines for Catalytic Organic

Transformations: Applications in Homogeneous and Polymer Supported Alkene

Isomerization, and Hydrogen Deuterium Exchange

by

Gulin Erdogan

Doctor of Philosophy in Chemistry

University of California, San Diego, 2012

San Diego State University, 2012

Professor Douglas B. Grotjahn, Chair

The research covered in this thesis involves studying and understanding the

behavior of bifunctional ligands, specifically imidazolylphoshines. The major field of

study is reaction of cyclopentadienyl ruthenium complexes with olefins, namely alkene

isomerization. In these complexes, the basic nitrogen of the imidazolylphosphine is

thought to deprotonate coordinated alkene intermediates reversibly, facilitating

isomerization of terminal alkenes to yield internal alkenes selectively. The CpRu alkene

isomerization catalyst is capable of moving double bonds as far as 30 positions; further

mechanistic studies in presence of deuterium labeling as a tool, has led to development of

hydrogen deuterium exchange of olefins at allylic positions. This finding supports the

xxv

proposed mechanism and provides and outstanding deuteration at positions accessible by

isomerization. The alkene isomerization catalyst can be used in a two-phase setting where

the catalyst is dissolved in the organic layer and the non-toxic, non-flammable isotopic

source (D2O) is immiscible with the organic layer. Using biphasic settings one can

literally wash out reactive protons on the substrate without using organic solvents.

In order to control high activity of alkene isomerization catalyst in absence of

steric bulk provided by the substrate, bulkier phosphine ligands were synthesized and the

activity of their metal complexes toward linear olefins was investigated. As a result, a

family of catalysts that is capable of isomerizing unsubstituted linear alkenes to various

mixtures have been established, where one can choose a complex to fit the needs of the

process at hand. Further investigation with terminal alkenes bearing functional groups

can be carried out to investigate whether mono-isomerization will still be the major

transformation taking place, which is expected to give access to high-value 2-alkenes.

To provide easy product-catalyst separation and potential wider application, the

first syntheses of polymer-supported imidazolylphophines were developed, and the

alkene isomerization catalyst was thus immobilized on polystyrene-based Merrifield

resin. Compared to the homogeneous catalyst, the immobilized catalysts give the same

high (E)-selectivity and conversion in isomerizations of terminal olefins to internal

olefins with very low metal leaching from the insoluble support. Furthermore, use of

organic solvents can be excluded and isomerization can be carried out in neat liquid

organic substrates.

1

CHAPTER 1

BIFUNCTIONAL CATALYSIS

2

Berzelius first introduced the term catalyst in 1835 and today the contribution of

catalysis towards the global gross domestic product is about 35 %.1 More than 90% of

chemical and refining processes use catalysts2 and the world is dependent on catalysts for

food, fuel, plastics, synthetic fibers, and many other everyday commodities. The global

demand for catalysts in 2010 was estimated at approximately 29.5 billion US dollars and

~850,000 tons in 2007. The worldwide annual demand for catalysts has been projected to

increase by 3.5-4% annually through 2012.3

A catalyst accelerates a reaction without being consumed in the process, ensuring

more efficient use of resources, and maximizing and optimizing the output of a process.

Catalysis is essential to our ability to control chemical reactions, including those involved

in energy-related transformations. Catalysis is therefore integral to solving current and

future energy problems and a key to our sustainability.

Catalysts vary in composition from solid metal surfaces to gases. Traditionally,

heterogeneous catalysts have been used for the large-scale production of commodity

chemicals due to their robust nature and ease of separation. In contrast, homogenous

catalysts offer high selectivity, the ability to produce pure products in high yield and are

easier to modify in order to control a reaction. Although the broad use of soluble metal

complexes did not begin until the 1940s their superiority mentioned above led to

extensive use of homogenous catalysis in industry for syntheses of organic compounds.

Today homogenous catalysis is responsible for worldwide production of commodities

3

like adiponitrile via but-1,3-diene hydrocyanation (Du Pont), detergent range alkenes via

Shell Higher Olefins Process (SHOP), poly(ethylene terephtalate) (PET) via

polycondensation of terephtalic acid with ethylene glycol.4

The wider application of homogenous catalysis is closely related to in-depth

understanding of the chemistry involved. The ease of the mechanistic investigation of

homogeneous catalysts is a distinct advantage, opening rational ways to develop novel

and superior catalysts. In conventional metal-based homogeneous catalysts, catalysis is

essentially performed at the metal center, with the ligands not actively participating in

bond-making and -breaking of the substrate(s). However, there is a special class of

catalysts that operates by cooperation between the metal center and surrounding ligands,

referred to as bifunctional catalysts.

Examples of bifunctional catalysts are widely found in biological systems. Liver

alcohol dehydrogenase (ADH) catalyzes the oxidation of primary and secondary alcohols

and can also catalyze the reverse reaction, reduction of respective aldehydes and ketones.

In humans, alcohol dehydrogenase exists as a dimer, in multiple forms divided into five

classes. The enzyme is present in the liver and the lining of the stomach in high

concentrations. The active enzyme is a dimer of identical subunits and each subunit has

two domains, the catalytic active-site domain and the coenzyme-binding domain.5

Figure 1.1 Reaction catalyzed by LADH, oxidation of ethanol

The active site (Figure 1.2) consists of a zinc atom, His67, Cys174, Cys46, Ser48,

His51, Ile269, Val292, Ala317, and Phe319. The zinc is coordinated by Cys46, Cys174,

4

and His67 along with a water molecule, which is thought to be displaced by the alcohol

substrate. Phe319, Ala317, His51, Ile269 and Val292 appear to stabilize NAD+ by

forming hydrogen bonds. Zinc is considered to act as a Lewis acid on the complexed

alcohol molecule or carbonyl group of the aldehyde, facilitating the deprotonation of

alcohol or nucleophilic attack on a carbonyl group. In the classical mechanism, the

alcohol is thought to be deprotonated by Ser48 and the proton transported out of the

active site via a hydrogen bond network involving NAD+ and His51. Hydride transfer

from the α-carbon of alcohol to NAD+ would result in zinc-bound aldehyde or ketone and

NADH, and release of these products are considered the final steps in the catalytic

cycle.5,6

Figure 1.2. Alcohol dehydrogenase mechanism of action in active site

Another example of a bifunctional catalyst is galactose oxidase, a fungal secretory

enzyme which is one of the best-characterized free-radical enzymes. Galactose oxidase

5

has found use in quantitative determination of galactose in blood and other biological

fluids.7-9 The overall reaction catalyzed (Figure 1.3) is oxidation of a primary alcohol to

aldehyde coupled with reduction of oxygen to hydrogen peroxide.

Figure 1.3. Oxidation of D-galactose to D-galacto-hexodialdose

The crystal structure of galactose oxidase10 shows (Figure 1.4) that the Cu(II)

center is bound to two histidine and two tyrosine residues and a water molecule in a

square pyramidal fashion. One of the tyrosine ligands is bound axially and can act as a

general base, while the other is cross-linked to a cysteine residue, forming a Tyr-Cys

dimer. A tryptophan residue is stacked over the Tyr-Cys dimer and is thought to

contribute stabilization of the free radical formed.

Figure 1.4. Organization of the galactose oxidase active site

The mechanism proposed (Figure 1.5) predicts that galactose replaces the water

molecule in the equatorial position and proton from the alcohol is transferred to the axial

6

tyrosinate (Tyr495). Next, a hydrogen atom is transferred from the substrate to the

equatorial Tyr-Cys dimer radical and resulting species is oxidized through electron

transfer to the copper center yielding Cu(I) and aldehyde. Finally, Cu(I) and tyrosine are

reoxidized by oxygen to regenerate Cu(II) and give hydrogen peroxide. The oxygen

reduction half reaction is less well-characterized and proposed to involve a

hydroperoxide adduct (F) which may be protonated at the proximal oxygen (G) and give

the hydrogen peroxide product.11,12

Figure 1.5. Reaction mechanism proposed for galactose oxidase

The design of synthetic bifunctional catalysts has frequently been based on

mimicking biological systems.13-21 Shvo’s hydride catalyst22,23 reported in 1985 is one of

7

the earlier examples of metal-ligand cooperating bifunctional catalyst. The diruthenium

complex is activated by heat and dissociates into two catalytically active monoruthenium

complexes, an 18 e- complex that can be isolated and a 16 e- complex that has never been

directly observed, these two species are thought to interconvert throughout the catalytic

cycle. The 18 e- complex is proposed to simultaneously transfer hydride from the metal

center and a proton from the hydroxyl group on the cyclopentadiene ligand to

hydrogenate a ketone or imine. Subsequently, the 16 e- species formed would act as a

dehydrogenation catalyst to give a new molecule of 18 e- complex. The mechanism has

been extensively studied and recent reviews have been published on applications24-27 and

mechanism26,28,29 of Shvo’s catalyst and related species.

Figure 1.6. Shvo’s catalyst and proposed bifunctional mechanism

The Nobel Prize recipient in 2001, Ryoji Noyori, developed a bifunctional

ruthenium catalyst based on metal and N-H acid base cooperation for asymmetric

hydrogenation of ketones and imines. The hydrogen transfer between an alcohol and a

ketone is thought to take place reversibly through a six-membered pericyclic transition

8

state (Figure 1.7). The amido Ru complex would dehydrogenate an alcohol leading to the

amine hydrido complex, which in turn would react with carbonyl compounds to transfer

the hydride and a proton to the carbonyl yielding the alcohol product. When formic acid

is used for the asymmetric reduction, the reaction proceeds irreversibly with kinetic

enantioselection, in principle 100% conversion.18,30-33

Figure 1.7. Noyori’s catalyst and proposed bifunctional mechanism

More recently, Milstein reported a new mode of bond activation by metal-ligand

cooperation based on dearomatization-aromatization of pyridine- and acridine-based

heteroaromatic pincer complexes (Figure 1.8). Deprotonation of a pyridinyl methylene of

the pincer ligand can lead to dearomatization, and the resulting complex can activate a

chemical bond H-Y where Y can be H, OR, NR2 or C, by cooperation between the ligand

and the metal, without changing the oxidation state of the metal. These types of

complexes can be catalytically used in conversion of alcohols into esters and

dihydrogen,34 synthesis of amides from alcohols and amines,35 coupling of alcohols with

9

amines to form imines and dihydrogen,36 selective synthesis of primary amines from

alcohols and ammonia,37 hydrogenation of esters to alcohols,38 and hydrogenation of

carbon dioxide to formate salts.39

Figure 1.8. Dearomatization and aromatization of Milstein’s complexes

Catalysis research in the Grotjahn group focuses on complexes bearing a potential

hydrogen acceptor or donor present in the ligands. The bifunctional ligands most studied

in the Grotjahn lab are heteroaryl-substituted phosphines, in which the heteroaryl ring is

either five- or six-membered and includes one or more nitrogens, e.g. imidazole,

pyridine, pyrimidine, or pyrazole rings.40-47

In 2004, Lev44 et al. reported that cyclopentadienyl ruthenium complex 1.6

(Figure 1.9) developed in the Grotjahn group (now commercially available from Strem

Chemicals) catalyzes anti-Markovnikov alkyne hydration at 70 oC with initial TOF of

23.8 mol aldehyde per mol catalyst per hour. When the alkyne hydration is uncatalyzed

(70 oC, 5 equivalents of H2O), 1-nonyne did not hydrate to the ketone or the aldehyde

after 28 days.

10

Figure 1.9. Representative bifunctional complexes developed in the Grotjahn lab

The detection limit of this reaction was estimated to be 2 ppm; therefore, the rate

of the uncatalyzed reaction is less than 3 x 10-9 mol per hour, giving a half-life of at least

20,000 years. When hydration is catalyzed with a Brønsted-Lowry acid, e.g. HNTf2, the

ratio of ketone produced with respect to aldehyde is 33 to 1. Thus an upper bound for the

rate of aldehyde formation is 1 x 10-10 mol per hour. A half-life for aldehyde formation of

at least 600 000 years is estimated from the observation that under protic conditions the

appearance of aldehyde is 33 times slower than of the ketone. Since 1.6 gives initial TOF

of 23.8 mol aldehyde per mol catalyst per hour, a catalytic rate acceleration of >2.4 x 1011

was calculated. As for selectivity, there is no detectable ketone from the hydration of 1-

nonyne by 1.6 under conditions where one could detect one part ketone in the presence of

11

10,000 parts aldehyde. Thus, compared with protic catalysis, 1.6 changes the selectivity

of alkyne hydration by a factor of over 300 000.

Figure 1.10. Anti-Markovnikov alkyne hydration

In studying the origin of remarkable rate enhancements in alkyne hydration, the

presence of C-H-N hydrogen bonding in an alkyne π complex was revealed using NMR

coupling information, from both data within the alkyne ligand as well as between alkyne

and pyridine (2hJCN) (Figure 1.11). Scalar coupling across a hydrocarbon C-H bond (2hJCN

= 3 Hz) was part of showing that the C-H was engaged in a hydrogen bond with a ligand

nitrogen. Comparison made with the complex lacking the pendant nitrogens revealed the

difference in couplings observed involving the alkyne hydrogens. The 1JCC values of

both 1.7 and 1.9 are pointing to identical the similar electronic nature of both phosphine

ligands. The difference in 1JCH 1.7 and 1.9, combined with observation of 2hJCN of 1.7

strongly suggests presence of hydrogen bonding.48

12

Figure 1.11. Alkyne hydrogen bonding in intermediates related to anti-Markovnikov hydration

Hydrogen-bonding networks have been observed with complexes 1.2 and 1.3; in

the case of rhodium and iridium analogue of 1.3, X-ray structural data also supports the

binding of water and the hydrogen bonding to imidazole nitrogens. Both of these

complexes show moderate activity in base-free transfer hydrogenation of acetphenone by

2-propanol.45

Another lesson learned from anti-Markovnikov alkyne hydration is the importance of

steric bulk in close proximity to basic nitrogen on heterocycle. Comparison of complex

1.10 and its analogue 1.11 where C6 is bearing a hydrogen atom instead of tert-butyl,

aquo complex of 1.11 is not formed even upon heating up to 70 oC when 1000 equivalent

of water is present. Where as, 1.10-aquo is formed and 1.10 is quickly consumed with as

little as 5 equivalents of water at room temperature.49,50

13

Figure 1.12. Importance of pendant base substituents on structure and reactivity

In accordance to this observation, when hydration equilibrium of 1.2 analogues

1.12 and 1.13 was studied, the equilibrium shifts by 50-fold, from favoring chelation in

the case of 1.7 (Keq ~ 400 M-1) to aquo complex formation when C4 is substituted in 1.8

(Keq ~ 20,000 M-1).49

Figure 1.13. Hydration equilibrium of CpRu imidazolyl comlexes 1.12 and 1.13

Comparing carbonylation of 1.11 to 1.12 the observed half-lives are 15 minutes

and one day for imidazolyl pendant base and pyridyl pendant base, respectively. The

14

conclusion that can be drawn is, that the imizadole chleate opens more readily than the

pyridine chelate under the same conditions in absence of steric bulk around the chelating

basic nitrogen.

Figure 1.14. Comparison of pyridine and imidazole pendant base effect on chelate opening

The research covered in this thesis involves studying and understanding the

behavior of bifunctional ligands, specifically imidazolylphoshines, applying the lessons

learned from anti-Markovnikov alkyne hydration and looking for reactivity with

cyclopentadienyl ruthenium complexes with olefins is the major subject studied. The

mechanistic studies using deuterium labeling as a tool, has led to development of

hydrogen deuterium exchange of olefins at allylic positions. Unique activity and

selectivity of alkene isomerization catalyst, (Figure 1.15), has made it attractive for

organic transformations and as of April 2012 it is commercially available through Strem

Chemicals. The CpRu alkene isomerization catalyst (Figure 1.15) is capable of moving

15

double bonds as far as 30 positions; in order to tame its high activity in absence of steric

bulk provided by the substrate, bulkier phosphine ligands were synthesized and the

activity of catalysts made with them toward linear olefins has been investigated (Chapter

2). To provide easy separation and potential wider application, the alkene isomerization

catalyst has been immobilized on polystyrene-based Merrifield resin (Chapter 3). In the

search for new catalysts for arylamination, imidazolyl phophine complexes have been

used to investigate coupling reactions between halotoluenes and morpholine (Chapter 5).

Figure 1.15. Homogenous phase and polymer-supported alkene isomerization catalyst

16

REFERENCES

(1) Adams, C. Chem Ind-London 1999, 740.

(2) In R&D Magazine 2005; Vol. September.

(3) Market Reports: World Catalyst Market, 2008.

(4) Whyman, R. Applied organometallic chemistry and catalysis; Oxford University Press: Oxford ; New York, 2001. (5) Dolega, A. Coordin Chem Rev 2010, 254, 916.

(6) Hammes-Schiffer, S.; Benkovic, S. J. Annu Rev Biochem 2006, 75, 519.

(7) Frings, C. S.; Pardue, H. L. Anal Chem 1964, 36, 2477.

(8) Roth, H.; Segal, S.; Bertoli, D. Anal Biochem 1965, 10, 32.

(9) Hankin, L. J Assoc Off Ana Chem 1967, 50, 1342.

(10) Firbank, S. J.; Rogers, M. S.; Wilmot, C. M.; Dooley, D. M.; Halcrow, M. A.; Knowles, P. F.; McPherson, M. J.; Phillips, S. E. V. P Natl Acad Sci USA 2001, 98, 12932. (11) Que, L.; Tolman, W. B. Nature 2008, 455, 333.

(12) Whittaker, J. W. Arch Biochem Biophys 2005, 433, 227.

(13) Breslow, R. Accounts Chem Res 1995, 28, 146.

(14) Steinhagen, H.; Helmchen, G. Angewandte Chemie-International Edition in English 1996, 35, 2339. (15) van den Beuken, E. K.; Feringa, B. L. Tetrahedron 1998, 54, 12985.

(16) Rowlands, G. J. Tetrahedron 2001, 57, 1865.

(17) Clapham, S. E.; Hadzovic, A.; Morris, R. H. Coordin Chem Rev 2004, 248, 2201. (18) Ikariya, T.; Murata, K.; Noyori, R. Org Biomol Chem 2006, 4, 393.

17

(19) Das, S.; Brudvig, G. W.; Crabtree, R. H. Chem Commun 2008, 413.

(20) Natale, D.; Mareque-Rivas, J. C. Chem Commun 2008, 425.

(21) Grotjahn, D. B. Chem-Eur J 2005, 11, 7146.

(22) Blum, Y.; Shvo, Y. Israel J Chem 1984, 24, 144.

(23) Blum, Y.; Czarkie, D.; Rahamim, Y.; Shvo, Y. Organometallics 1985, 4, 1459. (24) Shvo, Y.; Czarkie, D.; Rahamim, Y.; Chodosh, D. F. J Am Chem Soc 1986, 108, 7400. (25) Karvembu, R.; Prabhakaran, R.; Natarajan, K. Coordin Chem Rev 2005, 249, 911. (26) Conley, B. L.; Pennington-Boggio, M. K.; Boz, E.; Williams, T. J. Chemical Reviews 2010, 110, 2294. (27) Samec, J. S. M. B., J. E. In Encyclopedia of Reagents for Organic Synthesis; Wiley: New York, 2008. (28) Samec, J. S. M.; Backvall, J. E.; Andersson, P. G.; Brandt, P. Chem Soc Rev 2006, 35, 237. (29) Comas-Vives, A.; Ujaque, G.; Lledos, A. J Mol Struc-Theochem 2009, 903, 123. (30) Noyori, R.; Yamakawa, M.; Hashiguchi, S. J Org Chem 2001, 66, 7931.

(31) Koike, T.; Ikariya, T. Adv Synth Catal 2004, 346, 37.

(32) Fujii, A.; Hashiguchi, S.; Uematsu, N.; Ikariya, T.; Noyori, R. J Am Chem Soc 1996, 118, 2521. (33) Uematsu, N.; Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J Am Chem Soc 1996, 118, 4916. (34) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J Am Chem Soc 2005, 127, 12429. (35) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007, 317, 790. (36) Gnanaprakasam, B.; Zhang, J.; Milstein, D. Angew Chem Int Edit 2010, 49, 1468.

18

(37) Gunanathan, C.; Milstein, D. Angew Chem Int Edit 2008, 47, 8661. (38) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. Angew Chem Int Edit 2006, 45, 1113. (39) Ben-Ari, E.; Leitus, G.; Shimon, L. J. W.; Milstein, D. J Am Chem Soc 2006, 128, 15390. (40) Grotjahn, D. B.; Brown, D. B.; Martin, J. K.; Marelius, D. C.; Abadjian, M. C.; Tran, H. N.; Kalyuzhny, G.; Vecchio, K. S.; Specht, Z. G.; Cortes-Llamas, S. A.; Miranda-Soto, V.; van Niekerk, C.; Moore, C. E.; Rheingold, A. L. J Am Chem Soc 2011, 133, 19024. (41) Grotjahn, D. B. Dalton Trans 2008, 6497. (42) Grotjahn, D. B.; Gong, Y.; DiPasquale, A. G.; Zakharov, L. N.; Rheingold, A. L. Organometallics 2006, 25, 5693. (43) Grotjahn, D. B.; Van, S.; Combs, D.; Lev, D. A.; Schneider, C.; Rideout, M.; Meyer, C.; Hernandez, G.; Mejorado, L. J Org Chem 2002, 67, 9200. (44) Grotjahn, D. B.; Lev, D. A. J Am Chem Soc 2004, 126, 12232. (45) Miranda-Soto, V.; Parra-Hake, M.; Morales-Morales, D.; Toscano, R. A.; Boldt, G.; Koch, A.; Grotjahn, D. B. Organometallics 2005, 24, 5569. (46) Miranda-Soto, V.; Grotjahn, D. B.; Cooksy, A. L.; Golen, J. A.; Moore, C. E.; Rheingold, A. L. Angew Chem Int Edit 2011, 50, 631. (47) Miranda-Soto, V.; Grotjahn, D. B.; DiPasquale, A. G.; Rheingold, A. L. J Am Chem Soc 2008, 130, 13200. (48) Grotjahn, D. B.; Miranda-Soto, V.; Kragulj, E. J.; Lev, D. A.; Erdogan, G.; Zeng, X.; Cooksy, A. L. J Am Chem Soc 2008, 130, 20. (49) Lev, D. A., University of California, San Diego and San Diego State University, 2004. (50) Grotjahn, D. B. Pure Appl Chem 2010, 82, 635.

19

CHAPTER 2

DEVELOPMENT OF NEW BIFUNCTIONAL

CYCLOPENTADIENYL RUTHENIUM

IMIDAZOLYL PHOSPHINE COMPLEXES FOR

CONTROLLED ALKENE ISOMERIZATION

20

INTRODUCTION

This chapter describes some of my experimental and computational efforts to

improve selectivity of bifunctional alkene isomerization catalysts developed in the

Grotjahn lab, followed by an overview of alkene isomerization challenges and scope.

Alkene isomerization is an atom-efficient reaction an a key step in major industrial

processes.1 It is used for in petrochemical refining processes and in the synthesis of linear

olefins in the SHOP process or adiponitrile preparation from butadiene and HCN, where

two isomerization steps are involved.2 Carbon-carbon double bond shift is also largely

employed in the synthesis of pharmaceuticals and fine chemicals such as flavors and

fragrances.3-6 Significant examples (Figure 2.1) are (i) enantioselective isomerization of

(E)- and (Z)-diethylgeranylamine to (R)-citronellal-(E)-enamine as the key

enantiodetermining step in synthesis of (-)-menthol on the scale of 3,000 tons per year by

Takasago International Corporation,7 (ii) 6-methyl-6-hepten-2-one isomerization in

vitamin A synthesis used by BASF,8 and (iii) the isomerization of allyl benzene

derivatives such as safrole, estragole, and eugenol to the corresponding internal alkenes

which are used to enhance flavor in food or beverages in industry.2

21

Figure 2.1. Selected alkene isomerizations involved in industrial processes

In the isomerization of allyl benzene derivatives, high selectivity for the (E)-

isomer is an important challenge since (Z)-isomers are characterized by an unpleasant

taste and sometimes a toxic nature, so highly pure (E)-products are required for market

(less than 1% (Z)-isomer content for human use). Currently, tedious purification steps are

required to separate the isomers, therefore there is an increasing interest in the

development of highly selective isomerization processes to reduce production costs. At

present, industrial isomerization of 4-allylanisole (estragole) to (E)-anethole is performed

with potassium hydroxide (KOH) at high temperatures (200 oC) with moderate yields of

about 56% and (E) to (Z) ratio of 82:18, while most fragrances reported above are still

obtained by extractions from natural sources with an overall annual production of several

million metric tons.9 Many more processes of alkene isomerization are a topic of

interest,10-22 hence selective olefin isomerization under mild conditions is a goal that

22

deserves increased attention from organometallic chemists.

Transition metal-catalyzed olefin isomerization in organic chemistry can be

achieved with many metals, across the periodic table. To name a few metals, Fe,23-30 Ir,30-

36 Pd,37-39 Ti,40-43 Ni,44-47 Rh,30,34,48-51 and Ru complexes are capable of carbon-carbon

double bond isomerization. Wilkins88on’s catalyst RhCl(PPh3)3, 2.1 (Figure 2.2), can be

employed in isomerization of allylic ethers to give enol ethers, which can hydrolyze to

give free alcohol and a carbonyl compound, becoming a method for removing the allyl

protecting group for alcohols.52-54

Figure 2.2. Isomerization by Wilkinson’s catalyst

Emerson and Pettit proposed the first examples of iron-catalyzed allyl alcohol

isomerization to propanal.55 Since then, many reports of alkene isomerization using iron

complexes, especially Fe(CO)5, have been published. Besides allylic alcohols, allyl

ethers, allyl benzene derivatives23 and homoallylic compounds that bear a variety

functional groups can be isomerized with Fe(CO)5.24 Recently, Beller et al. reported

Fe3(CO)12 enabling selective isomerization of terminal olefins to corresponding beta-

olefins in presence of other internal double bonds (80-100 oC, 3N KOH).56

23

Ruthenium based catalysts developed by Grubbs et al. have been widely used for

alkene metathesis, and isomerization of alkenes has been observed as a side reaction

caused by catalyst degradation. Ruthenium hydrides generated from 2.2 (Figure 2.3) can

effectively isomerize allylic bonds to the adjacent position under mild conditions.

Although the ruthenium hydride, 2.2-H, has been isolated by Nolan57 and Grubbs,58 it

hasn’t been exploited as an alkene isomerization catalyst. Later, studies by Nishida,59

Hanessian,60 and Rosa61,62 proved that 2.2-H can be successfully used for synthetic

transformations.

Figure 2.3. Isomerization of allyl groups by metathesis catalyst 2.2

24

Isomerization of allylic alcohols to corresponding aldehydes and ketones has been

extensively investigated heavily with rhodium and ruthenium complexes. A variety of

derivatives of ruthenium complexes were employed in early applications, for example

Ru(CO)3(PPH3)2 and RuCl2(PPh3)3, but a breakthrough was made by CpRu(PPh3)2Cl and

the corresponding indenyl complex in combination with Et3NHPF6 investigated by Trost

et al.63,64 As seen in Figure 2.4 and Table 2.1, the indenyl system 2.5 is more active than

the cyclopentadienyl system 2.4 possibly due to lowered energy of ring slippage from η5

to η3. Modifications of conditions were also explored to obtain amore active catalyst, for

example use of AgOTs instead of Et3NHPF6 for ionizing the chloride ligand resulted in a

turnover frequency number of 200,000 h-1.65 Isomerization of allylic alcohols proceeded

smoothly and isolated double bonds were not affected. Contrary to Trost’s suggestion,

unfunctionalized alkenes could also be isomerized with this system, although at a much

lower rate, for example, 1-octene can was isomerized to a mixture of 2-, 3-, and 4-

octene.65

Figure 2.3. Trost’s ruthenium complexes for allylic alcohol isomerization

25

Table 2.1. Isomerization of allylic alcohols by 2.4 and 2.5 at 100 oC in 1,4-dioxane with 10 mol% Et3NHPF6

Substrate Catalyst

(5 mol %) Time (h) Yield (%)

2.4 9 23

2.5 2 83

2.4 8 90

2.4 1.5 92

2.4 1 87

2.5 3 82

2.4 24 53

2.5 3 81

Slugovc et al.66 improved the activity of Trost’s cyclopentadienyl system by

exchanging the chloride ligand for a more labile acetonitrile ligand, which could

exchange for alkene substrate more readily (Figure 2.4). The use of 2.6 reduced reaction

times, for example in the case of 3-phenyl-2-propenol, complex 2.6 yielded the

corresponding carbonyl compound with TON = 760, TOF = 1815 h-1 (in 25 min with 0.12

mol % loading) while 2.4 performed with TON = 20 and TOF = 2.5 h-1 under similar

conditions. Another study done by Slugovc was varying the alkyl groups on the

26

phosphine ligands from phenyl to methyl and cyclohexyl, which showed the overall

better performance of alkyl phosphines. See several examples reported in Table 2.2.

Figure 2.4. Improved cyclopentadienyl ruthenium complexes for allylic alcohol isomerization by Slugovc.

Table 2.2. Isomerization of allylic alcohols by 2.4 and 2.5 at 57 oC in chloroform-d

Substrate Catalyst

(1 mol %) Time Yield (%)

2.6 30 min >98

2.7 8 min >98 2.8 5 min >98

2.6 3 min >98

2.7 90 min >98

2.8 3 min >98

2.6 17 h 91

2.7 15 h 87 2.8 17 h -

Although modifications introduced by Slugovc reduced reaction times, substrates

where the double bond was located further than allylic positions were not accessible or in

the absence of alcohol functionality, and oligomerization side products of the carbonyl

compounds were observed. In order to move double bonds over longer carbon chains

27

(nine or more positions) it has been necessary to use either stoichiometric or 0.9

equivalent of the metal per alkene in systems reported by Iranpoor67 and Gibson.68

In 2007, the Grotjahn group reported the discovery and development of a

cyclopentadienyl ruthenium complex that bears a nitrogen-containing heterocyclic

substituent on the phosphine ligand.69

Metal complexes containing hybrid P-N donor ligands have been extensively

investigated due to their potential hemilability. The combination of fundamentally

distinguished a P-ligand part which is a soft donor that exhibits π-acceptor properties

stabilizing low or medium oxidation state metals and a N-ligand part, which is a hard

donor, dominantly acting as a σ-donor more suitable for metals with higher oxidation

states. Many metal complexes with mixed donor ligands containing phosphorus as well

as sp2-N donors within heterocycles are known.70 The main focus has been on ligands

with phosphine-pyridine71-73 and phosphine-oxazoline donors,74-77 and only a limited

number of complexes containing bidentate phosphine-imidazolyl78-86 or phosphine-

imidazoline87-89 donors have been reported. Applications of metal complexes containing

phosphine imidazolyl or phosphine-imidazoline donor ligands in catalysis include the

Heck coupling reactions78,79 and the hydrogenation of alkenes87 and imines.89

Besides the attractive features mentioned above, the synthesis of imidazolyl

phosphines by SN2 replacement by 2-lithioimidazoles on commercially available

chlorophosphines could be performed with high yields in nearly all reactions, and pyridyl

phosphines are accessible from nucleophilic substitution with metallated pyridines,

therefore preparation of different analogues and library construction is straightforward.

28

Figure 2.5. CpRu precursor, pyridylphosphines and imidazolylphosphines used for catalytic alkene isomerization screening

In the Grotjahn group, catalytic alkene isomerization was screened with a library

of imidazolyl and pyridyl phosphine ligands (Figure 2.5) along with traditional

monofunctional phosphines such as PMe3, PCy3, PPh3, and PiPr2Ph, all using

cyclopentadienyl tris(acetonitrile)ruthenium(II) hexafluorophosphate,

[CpRu(CH3CN)3]PF6, 2.9, as the metal precursor and 1H NMR spectroscopy as the

detection technique. The two prototypical organic substrates 1-pentene and 4-penten-1-ol

were chosen to find catalysts that are capable of isomerizing alkenols that have the

alcohol functionality further than homoallylic position as well as isomerizing double

bonds that lack the potential thermodynamic stabilization provided by formation of a new

functional group (formation of aldehyde in this case). Reactions of the chosen substrates

were relatively easy to monitor with 1H NMR spectroscopy (there being only two

positional isomers for 1-pentene and three for 4-penten-1-ol) and previously reported

complexes, 2.4-2.8, were not successful at isomerizing these substrates.

29

Figure 2.6. Organic substrates used in catalytic alkene isomerization screening

Results of the screening revealed that several pyridyl- and imidazolylphosphines

were capable of isomerizing 1-pentene but not all the systems were capable of

isomerizing 4-penten-1-ol. The best ligand screened featured the imidazolylphosphine

with isopropyl groups on the phosphine and tert-butyl group on C4 and methyl on N1 of

the imidazole group (Figure 3.7). Details of this screening can be found in other theses

from the Grotjahn group.90,91 The resulting alkene isomerization catalyst 2.10 selectively

converts terminal alkenes to (E)-internal alkenes. In case of alkenols, substrates with

various chain lengths can be isomerized, culminating in achieving the world record to

date of moving an alkene over 30 bonds to form the corresponding ketone from the

starting alkenol.69,92

Figure 2.7. Alkene isomerization catalyst developed in Grotjahn research group

30

Table 2.3 shows substrates that represent the some of the scope of the alkene

isomerization catalyst. In all cases, 2.10 presents high selectivity towards formation of

(E)-alkenes, isomerization of allyl ether (Table 2.2, entry 4) gave (E, E)-propenyl ether in

high yield without Claisen rearrangement of the intermediate allyl propenyl ether93,94 and

without any detectable (Z, E)-isomer.

Table 2.3. Scope of alkene isomerization catalyst 2.10a

Substrate Product 2.10 (mol %) Time Temp

(oC) Yield (%)

2 15 min 25 95

2 5

1 h 1 d

70 25

95 95

2 4 h 25 75

2 40 min 25 96

5 4 h 70 90

n = 9, R = Me

5 4 h 70 97

2 2 h 70 96

5 2 h 25 86

n = 30, R = Me

30 3 d 70 81

a Acetone or acetone-d6 as solvent.

31

There are two major mechanisms which have been proposed for alkene

isomerization: (1) an alkene insertion mechanism that involves metal hydrides and goes

through alkyl intermediates (Figure 2.8) and (2) an allyl-hydride mechanism, which

involves π-allyl intermediates (Figure 2.9) formed through C-H activation. Both routes

are reversible; therefore, the products will reach thermodynamic equilibrium eventually.

In the alkene insertion route, a metal hydride binds to the alkene and undergoes

insertion to yield a metal alkyl complex (primary and/or secondary), then β-hydrogen

elimination from the metal-secondary alkyl complex can give both (E)- and (Z)-isomer of

the internal alkene. The initial (E)- to (Z) ratio (kinetic product) depends on the nature of

the catalyst but the final ratio depends on the thermodynamics. Ni(OPEt3)444

RhCl395

and

RhCl(PPh3)3 96-98 are examples of complexes that have been shown to behave in a manner

consistent with the alkene insertion mechanism.

Figure 2.8. Catalytic cycle for alkene insertion mechanism of isomerization

In the allyl-hydride route, the proposed mechanism involves π-allyl intermediates

formed by cleavage of an allylic C-H bond. This mechanism has been established for

32

Fe3(CO)12 and PdCl2(NCPh)2,99 a number of detailed mechanisms have been proposed

but the simplest is a 1,3-suprafacial shift in which an allylic hydrogen moves from C1 to

C3 in a coordinated olefin by way of direct metal-hydride interaction.

Figure 2.9. Catalytic cycle for allyl mechanism of alkene isomerization

The mechanism proposed for alkene isomerization proposed for 2.10 (Figure

2.10) starts with dissociation of the acetonitrile ligand, demonstrated by the observation

of ethylene binding (to form an ethylene analog of 2.11) when 25 equiv were added in

acetone-d6, displacing the nitrile but leaving the P,N-chelate is still intact. In the case of

alkenes with allylic hydrogens, formation of π-allyl complex is thought to be facilitated

by the nitrogen on the imidazole on the phosphine ligand, a concept supported by the

observation that a complex which lacks the pendant base is 330 times slower at

isomerizing 1-pentene and about 10,000 times slower in the case of 4-penten-1-ol.92 Also

bubbling propene into a solution of 2.10 in presence of deuterium oxide leads to H/D

exchange at the terminal positions but not the internal position (Chapter 4). The internal

33

hydrogen stays intact even after extended reaction times in the presence of active catalyst,

a fact that renders the alkene insertion mechanism highly unlikely, because it would

require an unprecedentedly high preference for forming a metal-primary alkyl

intermediate rather than the secondary isomer.

Figure 2.10 also explains the high (E)-selectivity observed, because intermediates

2.12-Z and 2.13-Z will be relatively higher in energy than 2.12-E and 2.13-E due to steric

constraints. Moreover, when terminal alkenes are isomerized to internal (E)-alkenes or

(E)-2-butene was left in presence of 2.10 some (Z)-isomer is observed after extended

periods (>>10 x more than the time reaction required; in one case, more than 3,000,000

times longer than the time of reaction required91) (Chapter 4).

Figure 2.10 Proposed mechanism of alkene isomerization with 2.10

Recent density functional calculations reported by Tao et al.100 proposed the

involvement of an allyl-hydride mechanism but still steps where hydrogen transfer may

occur via pendant nitrogen (Figure 2.11). The authors only consider the formation of (E)-

alkene, so do not address the origins of kinetic selectivity summarized above. Essentially,

34

the computed mechanism proceeds via 2.11, 2.12-E, and 2.13-E, but the steps between

2.12-E and the two other species named are thought to differ from the steps shown in

Figure 2.10. According to this study isomerization of 1-pentene proceeds as follows: (1)

formation of agostic intermediate 2.14 and then the β-H elimination to generate a Ru-H

intermediate (2.15), (2) (formally) reductive transfer of the hydridic hydrogen to the

pendant base N and produce a π-allyl intermediate (2.12-E), (3) rotation to place the N-H

moiety at the other end of the π-allyl system, (4) oxidative transfer of the NH to Ru to

generate corresponding Ru-H intermediate (2.17), (5) reductive elimination to eventually

generate 2-pentene. It is proposed that the function of the imidazole pendant base is

transportation of H between hydride intermediates but the transition state of allylic proton

transfer directly to the pendant nitrogen was not located. These calculations do not

explain the geometric

Figure 2.11. Proposed mechanism by Tao et al.

selectivity towards (E)-alkenes but still explain the acceleration experimentally observed

due to presence of pendant base.

35

Part of my thesis research seeks to improve or tailor the selectivity of 2.10

through ligand design. Efforts to rationalize the alkene isomerization mechanism through

computational mechanistic studies are ongoing in the Grotjahn research group. Looking

at preliminary calculations, which I performed, the geometric selectivity can be explained

by iso-propyl groups on the phosphine ligand occupying the space that would likely to be

occupied by a (Z)-alkene formed. In contrast, the upper left quadrant is sterically open for

the forming (E)-alkene to fit. A complete explanation of geometric selectivity would

involve calculations with a bound alkene (e.g 1-pentene) in all possible conformations,

not just the one shown.

Figure 2.12. Computational model of propene (shown with yellow colored carbons) formed after loss of CH3CN from alkene isomerization catalyst 2.10

Taking into consideration the steric constraints iso-propyl groups on phosphine

would impose during isomerization, analogues of 2.10 with bulkier phosphorus

substituents could be anticipated to be slower catalysts. This is consistent with

36

observations in earlier screening of catalytic alkene isomerization: when tert-butyl groups

were present on the phosphine only a trace amount of 2-pentene was observed at room

temperature after 24 h,.90,91 whereas 2.10 completes this process within 15 min. Thus,

bulky groups R1 on phosphorus may impede alkene binding, as just mentioned;

alternatively, it is known from work of Yi Gong in the Grotjahn lab that large R1 groups

impede opening of (imidazolyl)phosphine chelates, likely through an analog of the

Thorpe-Ingold effect.101,102

Along with the phosphine substituents R1 (Figure 2.13), imidazole substituents

can be used to tune the catalyst by introducing variations in key positions. The α-position

to the basic nitrogen provides steric control by introducing bulky groups (R3) that should

influence access to the basic lone pair (see Chapter 1, Figure 1.12, 1.13 and related

discussion). The basicity of the lone pair can also be altered by substitutions (R2) of the

non-basic nitrogen of imidazole. Substitution of the non-basic nitrogen can also provide

further remote steric control of the corresponding metal complex formed.103

Figure 2.13. Sites for tuning of imidazolylphosphine ligands and catalysts

The effect of increased steric hindrance at the phosphorus (Figure 2.13, R1), and

C4 position of imizadole (R3), was investigated with a series of imidazolylphosphines

including four new examples which I made with cyclohexyl, tert-butyl, and adamantyl

37

groups with 4-tert-butyl-1-methyl-imidazole that were synthesized along with iso-propyl

and tert-butyl phosphines of 4-adamantyl-1-methyl-imidazole. Facile complexation with

[CpRu(CH3CN)3]PF6 in acetone at room temperature yielded yellow-brown solids after

removal of solvents in good yields.

Figure 2.14. Alkene isomerization catalyst and its more sterically hindered analogues

In order to assess the effects of ligand sterics on structure, X-ray structures of

close analogs of 2.19 and 2.20 were obtained. Crystals suitable for diffraction were

obtained by using anion exchange: 2.19 was converted to 2.26 using tetrakis(3,5-

bis(trifluoromethyl)phenyl)borate [B[3,5-(CF3)2C6H3]4−] and 2.20 converted to 2.27

using tetrakis(pentafluorophenyl)borate [B(C6F5)4-]. Chelation of the basic imidazole

nitrogen was observed as in 2.10. Having tert-butyl groups on the phosphorus lengthens

the ruthenium phosphorus bond (Ru - P), and perhaps in compensation shortens the

38

chelate bond length, Ru – NIm and lengthens the bond length between phosphorus and

imidazole C2 carbon (P - CIm). The biggest change seen with bond angles is the

narrowing of the angles around phosphorus in chelate, complementary to the changes in

bond lengths mentioned (Table 2.4).

Table 2.4. Important bond lengths and angles for 2.10, 2.26, and 2.27

Bond Length 2.10 (PiPr2) 2.26 (PCy2) 2.27 (PtBu2)

P - CIm 1.808(4) 1.807(5) 1.814(4), 1.828(4)

Ru - NIm 2.202(4) 2.212(4) 2.194(3), 2.175(3)

Ru – P 2.3440(12) 2.330(6) 2.3957(9), 2.4183(9)

Ru - NAcetonitrile 2.064(4) 2.057(4) 2.055(4), 2.056(4)

Ru – Cpcenteroid 1.799 1.799 1.803, 1.811

Bond Angles 2.10 (PiPr2) 2.26 (PCy2) 2.27 (PtBu2)

NIm - Ru - P 67.46(9) 66.75(10) 66.95, 66.68 (8)

Ru - P - CIm 83.83(14) 84.09(15) 82.75(12), 82.09(12)

Ru - NIm - CIm 102.0(2) 101.9(3) 102.9(2), 105.1(3)

P - CIm - NIm 106.1(3) 105.3(3) 106.1(3), 106.0(3)

39

Figure 2.15. X-ray crystal structure of 2.26, hydrogens and counter anion hidden for clarity

40

Figure 2.16. X-ray crystal structure of 2.27, hydrogens and counter anion hidden for clarity

Selective isomerization of terminal alkenes to 2-alkenes is a valuable technique,

because 2-alkenes are of higher commercial value than terminal alkenes and they are

naturally scarce.104,105 Also, commercially more valuable even-numbered terminal

alkenes can be produced from odd-numbered terminal alkenes by selective mono-

isomerization followed by ethenolysis. For example, 1-nonene can be isomerized to 2-

nonene and ethenolysis of 2-nonene will give two commercially viable products, 1-octene

and propane.106 Moreover, alkene chains of various lengths can be accessed after

metathesis of the isomerized alkene. Controlled mono-isomerization of linear alkenes

devoid of functional groups have been achieved by few systems107-111 and most recently,

41

Jennerjahn et al. have demonstrated use of 1 mol % Fe3(CO)12 in presence of H2O/KOH

in diglyme at 80 oC for isomerization of 1-octene to 2-octene, but the geometric

selectivity is poor (E/Z = 5).56

In order to investigate controlled mono-isomerization of alkenes in absence of any

functional group influence, 1-heptene was studied instead of 1-hexene or 1-octene,

because: (1) heptene has only three positional isomers instead of four positional isomers

like octene, which makes identification of reaction mixture easier, and (2) heptene

isomers have a greater difference of product distribution between the positional isomers

than hexene. Product distribution based on enthalpies of heptene isomers was reported

previously (Table 2.5).112 If only the terminal isomer and the two internal (E) isomers are

possible, the proportion of the three components in this system would be 0.9, 54.1, and

45.0 % (last column of Table 2.5).

Table 2.5. Calculated product distribution of heptenes

Isomers

ΔHf

(kcal

mol-1)

Calculated

(%)

Experimental

(%)

System of only 1-, (E)-2-

and (E)-3- (%, calculated

from experimental)

1-heptene -23.35 0.427 0.728 0.9

(E)-2-heptene -25.31 11.743 12.724

(Z)-2-heptene -26.15 48.525 43.254 54.1

(E)-3-heptene -25.00 6.939 7.262

(Z)-3-heptene -25.91 32.366 36.032 45.0

Isomerization of 1-heptene (0.5 mmol) was carried out with complexes, 2.10, 2.19

- 2.23 with 2 mol % catalytic loading at room temperature and at 70 oC with total reaction

42

volume of 1 mL acetone-d6 in a resealable J. Young NMR tube. At room temperature,

terminal alkene 1-heptene was converted to (E)-2-heptene selectively with 2.10 and 2.19

(Table 2.6) with similar rate and both systems reached thermodynamic equilibrium in

about 30-40 min (entries 2 and 3). In sharp contrast, 2.20 and 2.23 (room temperature

data in Table 2.17 and 2.22, respectively) transformed about less than 2 % 1-heptene to 2-

heptene, showing that expansion to tert-butyl groups from iso-propyl groups have a

dramatic effect on rate of isomerization.

When isomerization was carried out at 70 oC with 2.20, 18 % 2-heptene (E/Z ~10)

and less than 1 % of 3-heptene was observed in one hour with 83 % 1-heptene still

present. After 23 h, the mixture still hadn’t reached thermodynamic equilibrium among

positional isomers (86 % 2-heptene, about 11 % 3-heptene and 4 % 1-heptene), although

the ratio of (E)- to (Z)-2-heptene had decreased from 10 : 1 to 6 : 1, showing a very slow

approach to the thermodynamic ratio of 3.4 : 1. The amounts of isomers were calculated

from 1H NMR integrations of peaks that were assigned to positions labeled in the

structures in Figure 2.17. Experimentally, it was impossible to discriminate the (E)- and

(Z)-isomers of 3-heptene, but it was possible to see separate (though closely spaced)

peaks for isomers of 2-heptene. The estimation of (Z)-2-heptene can be overestimated

about 5 % due to partial overlap of allylic methyl peaks.

43

Figure 2.17. Heptene isomers with CH3 or CH2 groups used for NMR integrations highlighted

Comparing entry 6 with entry 4, isomerization of 1-heptene sped up to 52 % 2-

heptene (E/Z ~ 9.5) and 3 % 3-heptene formation with 44 % of 1-heptene (20 min) when

steric bulk of groups on phosphine was increased from tert-butyl (2.20) to adamantyl

(complex 2.21, Table 2.6). The thermodynamic ratio of positional isomers was not

attained in 35 h (2 % 1-heptene, 76 % 2-heptene, 23 % 3-heptene) at 70 oC, although the

ratio of (E)- to (Z)-2-heptene had increased from 9.5 : 1 to 4 : 1 (versus theromodynamic

ratio of 3.4 : 1). Possibly, the increased steric bulk of phosphine ligand had increased the

strain of the chelate, which may lead to relatively more facile opening of the chelate,

therefore isomerization. The loss of geometric selectivity of the (E)-isomer may be

explained by possible lengthening of the P-Ru and bond, which may affect the spatial

arrangement of the active site and alleviate crowding so that there is space for the (Z)-

isomer to fit.

The presence of iso-propyl and iso-propyl like groups (e.g. cyclohexyl) on

phosphorus consistently leads to (E)-selective isomerization of 1-heptene, use of 2.22

where tert-butyl group on C4 position of the imidazole group on the phosphine ligand

was replaced with an adamantyl group, 79 % (E)-2-heptene, and 18 % 3-heptene was

formed, with 2 % 1-heptene still present in 9 minutes at room temperature.

44

Thermodynamic ratio of positional isomers was reached in 50 minutes (Table 2.6).

Table 2.6. Collective isomerization data of 1-heptene, and equilibrium composition predicted from Table 2.5

Catalyst (R1)2P R3 on

Im

Temp

(oC)

Entry Time

1-

(%)

2-

(%)

2-

(E:Z)

3-

(%)

Predicted if all 5 isomers are at equilibrium 0.7 56.0 3.4 : 1 43.3

Predicted if only 1-, (E)-2- and (E)-3- are at

equilibrium 0.9 54.1 - 45.0

1 15 min 1.4 67.7 >20 : 1- 28.5

2.10 i-Pr t-Bu 25 2 40

min 1.2 54.1 >20 : 1- 42.5

2.19 Cy t-Bu 25 3 30 min 1.2 60.1 >20: 1 36.5

4 1 h 82.6 17.7 9.7 : 1 <1 2.20 t-Bu t-Bu 70

5 23 h 3.5 85.1 6.0 : 1 11.3

6 20 min 43.6 52.1 9.5 : 1 3.2

2.21 Ad t-Bu 70 7 35 h 1.6 76.0 4 :1 23.3

8 9 min 1.6 79.0 > 20 : 1 17.8

9 12 min 1.5 75.4 > 20 : 1 22.0 2.22 i-Pr Ad 25

10 50 min 1.2 55.3 > 20 : 1 43.0

11 20 min 11.4 79.0 9.7 : 1 10.0

2.23 t-Bu Ad 70 12 11 h 1.8 77.3 5.8 : 1 22.1

Some difference in activity between 2.10 and 2.22 (R3 on imidazole = tert-butyl

versus adamantyl, respectively) can be acknowledged when looking at the isomerization

of 1-heptene at early stages (Table 2.6): using 2.10, in 15 min, the reaction mixture

composition was 2 % 1-heptene, 68 % 2-heptene, and 29 % 3-heptene in which the

45

thermodynamic ratio of positional isomers was reached in 40 min. In contrast, using

2.22, in a similar time frame (12 min) afforded 2 % 1-heptene, 76 % 2-heptene, and 22 %

3-heptene, and the thermodynamic ratio of positional isomers was reached in 50 min.

More rapid conversion of 2-heptene in case of 2.22 compared to 2.10 could be explained

by the adamantyl group rendering the N-chelate more labile due to steric bulk in close

proximity, though the differences are modest.

Finally, when comparison of 2.20 and 2.23 is made, where tert-butyl group on C4

position of the imidazole group on the phosphine ligand was replaced with an adamantyl

group, reactions at 70 oC show stark difference. Starting 1-heptene is quickly consumed

by 2.23 (entry 11), but 2.20 holds on to the terminal alkene for over 1 h (entry 4): 83 %

and 3 % 1-heptene is present at one-hour mark with 2.20 and 2.23, respectively.

Distinctive (E)- and (Z)-heptene ratios were observed: although one can obtain 79 % 2-

heptene with 9.7 E/Z ratio in 20 min with 2.23 (entry 11), complex 2.20 (entry 5) after

nearly one day provides a higher yield of 2-heptene (85 %) with a mixture of E/Z ratio of

6 to 1.

In summary, from all of the entries in Table 2.6, it appears that the most

promising ones as far as maximal amount of (E)-2-heptene are entries 5, 11, and 8, with

the first two (both featuring catalysts with tert-butyl on P) being the most favorable.

Alkene isomerization of 1-hexene and 1-decene with 2.20 at 70 oC is consistent

with 1-heptene isomerization, as well as 1-hexene isomerization with 2.23 at room

temperature.

In conclusion, mono-isomerization of linear alkenes were investigated with a

group of CpRu complexes bearing imidazolyl phosphine ligands with varying steric

46

hindrance at the phosphorus and imidazole C4 positions. Cyclohexyl groups on

phosphorus behave very much like isopropyl groups; similar rate of isomerization and

(E)-selectivity is observed. Alkene isomerization is slower and more selective towards

mono-isomerization when the phosphorus atom bears tert-butyl groups, but modification

to bigger substituents leads to acceleration of isomerization arguably due to increased

strain applied to chelate ring formed by increased length of Ru-P bond distance. Effect of

C4 substitution is observed in form of acceleration of isomerization when the substituent

is so sterically big that the Ru-N chelate opening is quicker due to elongated Ru-N

distance. As a result, a family of catalysts that is capable of isomerizing alkenes to

various mixtures have been established, where one can choose a complex to fit the needs

of the process at hand.

Further investigation with terminal alkenes bearing functional groups can be

carried out with 2.20 to investigate whether mono-isomerization will still be the major

transformation taking place, which is expected to give access to high-value 2-alkenes.

The next chapters deal with very different optimizations of the bifunctional alkene

isomerization catalysts, fully exploring a novel heterogenized version of 2.10 in Chapter

3 and the ability of homogeneous catalyst 2.10 to perform H/D exchange in Chapter 4.

47

EXPERIMENTAL SECTION

Manipulations were carried out in a nitrogen-filled glovebox or using Schlenk techniques.

Acetone-d6 from Cambridge Isotope Laboratories, Inc. was further deoxygenated by

bubbling N2 gas through the liquid prior to use. Chloroform-d was dried by stirring over

calcium hydride for 1 d and vacuum transfer followed by freeze-thaw cycles to degas.

THF and ethyl ether were distilled over sodium metal and benzophenone indicator and

deoxygenated by bubbling N2 gas through them. NMR spectra were obtained at 30 °C on

either a 500-MHz INOVA (500 MHz listed below for 1H = 499.940 MHz and 125.7 MHz

for 13C = 125.718 MHz), a 400-MHz Varian NMR-S (400 MHz listed below for 1H =

399.763 MHz and 100 MHz for 13C = 100.525 MHz) spectrometer. 1H NMR chemical

shifts are reported in parts per million downfield from tetramethylsilane and referenced to

solvent resonances (1H NMR: 2.05 ppm for acetone-d6). 1H NMR signals are given

followed by multiplicity, coupling constants J in Hertz, integration in parentheses. For

complex coupling patterns, the first coupling constant listed corresponds to the first

splitting listed, e.g. for (dt, J = 3.2, 7.9, 1 H) the doublet exhibits the 3.2 Hz coupling.

Tetrakis(trimethylsilyl) methane or 1,4-dioxane were used as internal standards for

accurate integration. All 1H NMR spectra were acquired using 16 scans with 20 sec

relaxation delay and 15o pulse width. 31P NMR chemical shifts were referenced to an

external 85 % H3PO4 (aq) capillary placed in the solvent. Elemental analyses were

performed at NuMega Laboratories (San Diego). X-Ray crystallographic data were

obtained at UCSD Chemistry and Biochemistry X-Ray facility.

48

Figure 2.18. Synthesis of 4-(tert-Butyl)-2-(di-iso-propylphosphino)-1-methyl-1H--imidazole

4-(tert-butyl)-2-(di-iso-propylphosphino)-1-methyl-1H-imidazole (2.24). In a Schlenk

flask equipped with magnetic stirbar, 4-(tert-butyl)-1-methyl-1H-imidazole (8.4675 g,

0.0613 mol) was dissolved in 100 mL dry and deoxygenated THF and the flask was

placed in an acetone-Dry Ice bath at -78 °C. Using a syringe, an addition funnel was

charged with nBuLi in hexanes (42 mL of 1.52 M, 0.0638 mol) and the contents were

added to the reaction dropwise over 2.5 h. After 30 min, di-iso-propylchlorophosphine

(9.4256 g, 0.618 mol) was added dropwise using the addition funnel over 4.5 h. The

reaction was allowed to warm to room temperature and was quenched with deoxygenated

methanol until solution became clear yellow. Solvents were removed on a vacuum line

and the resulting solid was suspended in hexanes and the mixture filtered in the glovebox

through Celite. The filtrates were concentrated and the residue distilled under oil pump

vacuum, collecting the fraction distilling at 110 °C. Pure ligand was obtained as a clear

colorless liquid in 74.7 % yield (11.6451 g, 0.0458 mol). 1H NMR (400 MHz, acetone-d6)

δ 0.95 (dd, J = 7.0, 11.5, 6H), 1.05 (dd, J = 7.0, 16.0, 6H), 1.24 (s, 9H), 2.38 (sep of d, J

= 2.0, 7.0, 2H), 3.74 (d, J = 1.0, 3H), 6.83 (d, J = 2.0, 1H). 31P NMR (202 MHz, acetone-

d6) δ -18.5 (s) ppm.

49

Figure 2.19. Synthesis of 4-(tert-Butyl)-2-(di-cyclohexylphosphino)-1-methyl-1H--imidazole

4-(tert-butyl)-2-(di-cyclohexylphosphino)-1-methyl-1H-imidazole (2.25). In a Schlenk

flask equipped with magnetic stirbar, 4-(tert-butyl)-1-methyl-1H-imidazole (140.8 mg,

1.02 mmol) was dissolved in dry and deoxygenated THF (10 mL) and the flask was

placed in an acetone-Dry Ice bath at -78 °C. Using a syringe, nBuLi in hexanes (640 µL

of 1.6M, 1.03 mmol) was added to the reaction dropwise over 10 min. After 1 h, di-

cyclohexylchlorophosphine (262.8 mg, 1.13 mmol) was added dropwise using a gas tight

syringe over 25 min. The reaction was allowed to warm to room temperature and was

quenched with deoxygenated methanol until solution became clear and pale yellow.

Solvents were removed on a vacuum line and the resulting solid was suspended in

hexanes and the mixture filtered in the glovebox through Celite plug and fractions were

collected. Pure compound was obtained as a white solid, which was combined with the

product from a second run on identical scale. The total amount obtained was 315.9 mg

(47% yield). 1H NMR (400 MHz, acetone-d6) δ 1.24 (s, 9H), 1.90-1.00 (m, 30H), 2.2-

2.08 (m, 2H), 3.72 (d, J = 1.0, 3H), 6.81 (d, J = 2.0, 1H). 31P NMR (162 MHz, acetone-

d6) δ -27.4 (s) ppm. Elemental calculated for C20H35N2P (334.48) C, 71.82; H, 10.55; N,

8.38. Found C, 71.87; H, 10.38; N, 8.18.

50

Figure 2.20. Complexation of 2.25 to give 2.19

Complexation of 2.25 to give [CpRu (4-(tert-butyl)-2-(di-cyclohexylphosphino)-1-

methyl-1H-imidazole)(acetonitrile)]PF6 (2.19) In a glove box, ruthenium precursor

[CpRu(CH3CN)3]PF6 (217.3 mg, 0.500 mmol) was combined in a scintillation vial

equipped with a magnetic stir bar and deoxygenated acetone (4 mL). The phosphine,

2.25 (167.3 mg, 0.500 mmol) was added dropwise in deoxygenated acetone (3 mL), and

the resulting solution was allowed to stir overnight at room temperature under an

atmosphere of nitrogen. The solvent was removed in vacuo, without stirring, and the

residue left under vacuum until a flaky powder remained. The product was obtained as

yellow colored powder in 94.4% yield (360.5 mg, ~16 % bis-acetonitrile complex is

present). 1H NMR (500 MHz, acetone-d6) δ 1.37 (s, 9 H), 1.52-1.25 (m obscured by

neighboring peak, 10H), 1.96-1.68 (m, 8H), 2.25-2.12 (m, 2H), 2.51 (d, J = 1.5, 3 H),

2.60-2.54 (m obscured by neighboring peak, 1 H), 2.94-2.82 (m, 1H), 3.81 (s, 3 H), 4.60

(s, 5 H), 7.03 (s, 1 H) ppm. 31P NMR (202 MHz, acetone-d6) δ 27.42 (s) ppm. Elemental

calculated for C27H43F6N3P2Ru (686.66) C, 47.23; H, 6.31; N, 6.12. Found C, 47.32; H,

5.99; N, 6.60.

51

Figure 2.21. Anion exchange of 2.19

Synthesis of [CpRu (4-(tert-butyl)-2-(di-cyclohexylphosphino)-1-methyl-1H-

imidazole)(acetonitrile)]B[(3,5-(CF3)2C6H3)]4 (2.26) In a glove box, ruthenium

complex 2.19 (70.2 mg, 0.102 mmol) was combined in a scintillation vial equipped with

a magnetic stir bar and deoxygenated ethyl ether (4 mL). The salt, sodium tetrakis(3,5-

bis(trifluoromenthyl)phenyl)borate (93.1 mg, 0.105 mmol) was added dropwise in

deoxygenated ethyl ether (3 mL), and the resulting solution was allowed to stir overnight

at room temperature under an atmosphere of nitrogen. Deoxygenated water (8 mL) was

added to dissolve sodium hexafluorophosphate and excess sodium tetrakis(3,5-

bis(trifluoromenthyl)phenyl)borate, and the mixture was allowed to stir for 90 min. The

organic layer was separated and aqueous layer was washed with ethyl ether (3 x 5 mL).

The solvent was removed from combined organic layers in vacuo, without stirring, and

the residue left under vacuum until a flaky powder remained. The product was obtained

as yellow colored powder in 85.7 % yield (124.0 mg). Single crystals were obtained from

hexanes diffusion into THF solution of 3.26 at room temperature. X-ray analysis of

crystals revealed the structure. 1H NMR (400 MHz, acetone-d6) δ 1.36 (s, 9 H), 1.52-1.25

(m obscured by neighboring peak, 10H), 1.94-1.64 (m, 8H), 2.25-2.10 (m, 2H), 2.50 (s, 3

H), 2.60-2.54 (m obscured by neighboring peak, 1 H), 2.94-2.82 (m, 1H), 3.81 (s, 3 H),

52

4.60 (s, 5 H), 7.01 (s, 1 H) ppm, 7.66 (s, 4H), 7.79-7.78 (m, 8H). 31P NMR (162 MHz,

acetone-d6) δ 27.39 (s) ppm. 19F NMR (376 MHz, acetone-d6) δ -63.32 (s) ppm.

Table 2.7. Crystal data and structure refinement for 2.26

Empirical formula C59 H55 B F24 N3 P Ru

Formula weight 1404.91

Temperature 100(2) K

Wavelength 1.54178 Å

Crystal system Monoclinic

Space group C2/c

Unit cell dimensions

a = 19.0519(12) Å α= 90° b = 16.8814(10) Å β= 94.238(4)° c = 38.694(2) Å γ = 90°

Volume 12410.8(13) Å3

Z 8

Density (calculated) 1.504 g/cm3

Absorption coefficient 3.302 mm-1

F(000) 5680

Crystal size 0.08 x 0.02 x 0.01mm3

Crystal color, habit Yellow plate

Theta range for data collection 3.63 to 69.31°

Index ranges -22<=h<=22, -20<=k<=19, -36<=l<=46

Reflections collected 38189

Independent reflections 10849 [R(int) = 0.0358]

53

Table 2.7 Continued

Completeness to theta = 65.00° 97.0 %

Absorption correction Multi-scan

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 10849 / 0 / 975

Goodness-of-fit on F2 1.027

Final R indices [I>2sigma(I)] R1 = 0.0641, wR2 = 0.1653

R indices (all data) R1 = 0.0777, wR2 = 0.1782

Largest diff. peak and hole 2.032 and -0.485 e Å-3

Table 2.8. Atomic coordinates (x 104) and equivalent isotropic displacement parameters (Å2x 103) for 2.26. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.

______________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ Ru(1) 2666(1) 4053(1) 1083(1) 36(1)

P(1) 2297(1) 4732(1) 1561(1) 34(1)

F(31) 3613(4) 12257(4) 2087(3) 71(3)

F(31') 3800(30) 11840(60) 2019(9) 140(30)

F(32) 3226(5) 11747(7) 2538(2) 71(3)

F(32') 3190(30) 12080(50) 2436(18) 130(30)

F(33) 3897(3) 11093(4) 2241(2) 63(2)

F(33') 3650(40) 11040(30) 2390(20) 150(30)

F(34) 367(5) 11357(6) 1950(5) 91(5)

54

Table 2.8. Continued

______________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ F(34') 255(6) 11337(11) 1692(7) 97(7)

F(35) 868(4) 12454(6) 2003(3) 70(4)

F(35') 579(11) 11810(20) 2143(3) 134(14)

F(36) 593(5) 12005(8) 1513(2) 73(4)

F(36') 743(9) 12423(12) 1696(11) 156(17)

F(41) 4349(2) 11571(3) 796(1) 87(1)

F(42) 4107(2) 11512(3) 247(1) 90(1)

F(43) 4434(2) 10496(2) 531(1) 66(1)

F(44) 1102(2) 10974(2) 75(1) 89(2)

F(45) 961(2) 11793(2) 480(1) 69(1)

F(46) 1609(2) 12095(2) 78(1) 74(1)

F(51) -250(8) 7554(12) 1597(3) 106(6)

F(51') 130(30) 7319(12) 1668(11) 145(15)

F(52) -161(8) 8701(6) 1802(3) 81(4)

F(52') -448(14) 8320(30) 1652(12) 129(18)

F(53) 606(7) 7868(8) 1945(4) 82(5)

F(53') 480(20) 8200(40) 1992(8) 146(19)

F(54) 613(3) 7267(3) 415(1) 56(2)

F(54') 10(13) 7920(16) 337(6) 141(14)

F(55) -63(5) 8248(7) 348(4) 89(5)

F(55') 328(8) 9013(8) 214(3) 93(5)

F(56) 961(9) 8356(11) 207(4) 107(7)

F(56') 1072(12) 8181(18) 189(8) 76(8)

F(61) 3773(7) 7718(11) 587(4) 75(4)

F(61') 3820(20) 6860(30) 860(17) 149(19)

F(62) 4726(7) 7693(12) 903(5) 98(6)

F(62') 3920(30) 7930(40) 591(8) 140(17)

F(63) 4006(11) 6786(7) 926(3) 87(5)

F(63') 4744(17) 7590(30) 936(10) 102(15)

F(64) 4300(4) 7496(6) 2202(2) 80(4)

F(64') 4398(13) 8140(30) 2259(5) 105(19)

55


______________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ F(65) 3215(4) 7573(8) 2274(2) 99(5)

F(65') 3790(30) 7178(11) 2195(5) 113(19)

F(66) 3860(7) 8571(4) 2354(2) 88(4)

F(66') 3390(20) 8200(30) 2369(5) 110(20)

N(1) 2333(2) 5283(2) 963(1) 34(1)

N(2) 2151(2) 6365(2) 1259(1) 40(1)

N(3) 3639(2) 4583(2) 1093(1) 40(1)

C(1) 1909(4) 3254(5) 847(4) 104(4)

C(2) 2449(6) 3297(4) 633(2) 82(3)

C(3) 3034(4) 3029(5) 818(3) 101(4)

C(4) 2873(9) 2822(4) 1136(3) 126(5)

C(5) 2170(10) 2950(6) 1157(3) 134(6)

C(7) 2286(3) 5795(3) 340(2) 53(1)

C(8) 2270(4) 6600(4) 163(2) 69(2)

C(9) 1638(4) 5308(4) 211(2) 75(2)

C(10) 2954(4) 5374(4) 260(2) 65(2)

C(11) 2257(3) 5903(3) 727(1) 42(1)

C(12) 2147(3) 6566(3) 914(1) 46(1)

C(13) 2270(2) 5577(3) 1274(1) 34(1)

C(14) 2048(3) 6896(3) 1550(2) 48(1)

C(15) 1367(2) 4577(3) 1665(1) 43(1)

C(16) 1130(3) 5069(4) 1961(2) 56(1)

C(17) 358(3) 4866(5) 2022(2) 70(2)

C(18) -130(3) 4965(4) 1703(2) 64(2)

C(19) 120(3) 4475(4) 1407(2) 66(2)

C(20) 876(3) 4706(4) 1335(2) 50(1)

C(21) 2798(2) 4945(3) 1974(1) 37(1)

C(22) 2829(3) 4173(3) 2194(1) 46(1)

C(23) 3228(3) 4305(4) 2541(1) 48(1)

C(24) 3967(3) 4628(4) 2498(2) 56(1)

C(25) 3941(3) 5376(4) 2283(2) 55(1)

56


______________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ C(26) 3537(3) 5238(3) 1928(1) 44(1)

C(27) 4162(3) 4870(3) 1045(2) 47(1)

C(28) 4830(3) 5234(4) 970(2) 74(2)

C(31) 2219(2) 10332(2) 1573(1) 31(1)

C(32) 1577(2) 10723(3) 1607(1) 34(1)

C(33) 1522(2) 11372(3) 1820(1) 36(1)

C(34) 2093(3) 11657(3) 2021(1) 36(1)

C(35) 2735(2) 11275(3) 1996(1) 35(1)

C(36) 2795(2) 10640(3) 1776(1) 32(1)

C(37) 3369(3) 11589(3) 2211(1) 44(1)

C(38) 824(3) 11781(3) 1830(1) 46(1)

C(41) 2473(2) 10221(2) 940(1) 30(1)

C(42) 1930(2) 10612(3) 741(1) 35(1)

C(43) 2057(3) 11146(3) 485(1) 37(1)

C(44) 2743(3) 11321(3) 411(1) 39(1)

C(45) 3291(3) 10953(3) 603(1) 37(1)

C(46) 3159(2) 10419(2) 863(1) 32(1)

C(47) 4041(3) 11135(3) 544(2) 48(1)

C(48) 1422(3) 11512(3) 282(1) 45(1)

C(51) 1588(2) 9141(2) 1186(1) 32(1)

C(52) 1382(2) 8875(3) 855(1) 39(1)

C(53) 799(3) 8373(3) 788(2) 47(1)

C(54) 416(3) 8120(3) 1055(2) 48(1)

C(55) 617(2) 8366(3) 1387(1) 43(1)

C(56) 1188(2) 8868(3) 1453(1) 36(1)

C(57) 196(3) 8100(4) 1683(2) 54(1)

C(58) 579(4) 8111(6) 427(2) 80(2)

C(61) 2916(2) 9014(2) 1368(1) 28(1)

C(62) 3100(2) 8775(2) 1703(1) 29(1)

C(63) 3587(2) 8173(3) 1781(1) 34(1)

C(64) 3897(2) 7779(3) 1520(1) 36(1)

57


______________________________________________________________________________

x y z U(eq)

________________________________________________________________________________ C(65) 3714(2) 7998(3) 1182(1) 37(1)

C(66) 3238(2) 8604(3) 1106(1) 33(1)

C(67) 4060(3) 7578(4) 896(2) 57(2)

C(68) 3753(3) 7943(3) 2150(1) 42(1)

B(1) 2300(2) 9676(3) 1269(1) 30(1) ________________________________________________________________________________

Table 2.9. Anisotropic displacement parameters (Å2x 103) for 2.26. The anisotropic displacement factor exponent takes the form: -2p2[ h2 a*2U11 + ... + 2 h k a* b* U12]

______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

Ru(1) 42(1) 26(1) 40(1) -1(1) 3(1) 1(1)

P(1) 31(1) 34(1) 37(1) 0(1) 2(1) -1(1)

F(31) 69(4) 55(4) 86(6) 12(3) -19(4) -28(3)

F(31') 90(30) 260(80) 71(18) -70(40) 36(19) -130(40)

F(32) 54(4) 113(7) 45(3) -28(4) -1(3) -3(4)

F(32') 100(30) 150(50) 130(50) -120(40) -70(30) 40(30)

F(33) 42(3) 58(4) 85(5) -30(4) -24(3) 14(2)

F(33') 140(50) 140(40) 140(50) 50(30) -110(40) -50(30)

F(34) 46(5) 64(6) 169(14) 38(7) 55(8) 20(4)

F(34') 35(5) 95(11) 161(17) -52(13) 3(9) 26(6)

F(35) 49(4) 63(6) 96(7) -42(5) -15(4) 33(4)

F(35') 91(12) 260(40) 52(7) -21(12) 3(7) 108(18)

F(36) 56(5) 109(9) 52(4) -6(4) -9(3) 55(6)

F(36') 74(11) 73(13) 330(50) 120(20) 60(20) 41(10)

F(41) 60(2) 95(3) 108(3) -41(3) 14(2) -43(2)

F(42) 60(2) 109(3) 101(3) 57(3) 17(2) -14(2)

F(43) 45(2) 63(2) 93(3) 8(2) 22(2) -3(2)

F(44) 91(3) 57(2) 107(3) -14(2) -64(3) 16(2)

58


______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

F(45) 59(2) 78(2) 69(2) 16(2) 2(2) 33(2)

F(46) 73(2) 73(2) 74(2) 38(2) -7(2) 10(2)

F(51) 98(9) 129(13) 97(6) -35(7) 43(6) -89(9)

F(51') 180(30) 49(9) 230(30) 14(13) 140(30) -22(15)

F(52) 81(7) 78(5) 90(6) 13(4) 50(5) 22(5)

F(52') 62(12) 170(40) 160(30) 80(30) 50(15) 38(17)

F(53) 61(5) 112(8) 77(8) 47(7) 25(5) 13(6)

F(53') 140(30) 240(40) 65(11) -10(20) 15(17) -130(30)

F(54) 57(3) 49(3) 62(4) -24(2) 0(2) -10(2)

F(54') 160(20) 190(20) 73(12) 43(15) -48(14) -140(20)

F(55) 73(6) 112(9) 74(6) -26(6) -46(5) 38(7)

F(55') 107(10) 85(9) 81(9) 8(7) -30(7) -8(8)

F(56) 162(15) 117(11) 39(5) 2(6) -11(7) -94(11)

F(56') 54(8) 102(15) 73(12) -29(9) 4(7) 8(9)

F(61) 84(7) 90(8) 46(6) -31(6) -22(4) 53(5)

F(61') 69(16) 120(30) 260(40) -130(30) 34(18) -14(15)

F(62) 48(7) 165(13) 84(10) -63(9) 25(6) -6(8)

F(62') 270(40) 120(30) 35(12) 13(12) 48(19) 140(30)

F(63) 135(13) 43(5) 83(7) -12(5) 18(6) 50(7)

F(63') 70(18) 180(30) 55(13) -7(14) 4(10) 90(20)

F(64) 74(6) 113(9) 51(3) 22(4) -1(3) 65(6)

F(64') 75(16) 180(40) 58(12) 42(18) -34(11) -70(20)

F(65) 68(4) 170(13) 58(4) 64(6) -5(3) -29(6)

F(65') 230(60) 44(10) 64(12) 28(8) -20(20) 18(16)

F(66) 151(11) 68(4) 40(4) 1(3) -24(5) 21(5)

F(66') 140(30) 160(40) 48(12) 43(19) 39(17) 130(30)

N(1) 38(2) 28(2) 36(2) 0(2) -3(2) -1(2)

N(2) 38(2) 33(2) 47(2) -4(2) -1(2) 4(2)

N(3) 37(2) 33(2) 51(2) -3(2) 7(2) 5(2)

C(1) 56(4) 54(4) 200(12) -60(6) -7(6) -12(3)

C(2) 153(9) 42(3) 48(4) -19(3) -11(4) -16(4)

59


______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

C(3) 69(5) 56(4) 178(11) -68(6) 16(6) 4(4)

C(4) 243(15) 30(4) 92(7) -4(4) -69(9) 20(6)

C(5) 265(16) 48(5) 102(7) -30(5) 108(10) -80(8)

C(7) 72(4) 42(3) 43(3) 5(2) -6(3) -2(3)

C(8) 101(5) 51(3) 54(4) 8(3) 6(3) 7(3)

C(9) 96(5) 66(4) 59(4) -8(3) -16(4) -11(4)

C(10) 99(5) 53(3) 46(3) 5(3) 18(3) 6(3)

C(11) 49(3) 31(2) 44(3) 1(2) -4(2) 1(2)

C(12) 52(3) 33(2) 50(3) 5(2) -5(2) 2(2)

C(13) 28(2) 33(2) 41(3) -1(2) 2(2) -2(2)

C(14) 50(3) 32(2) 61(3) -10(2) 8(2) 2(2)

C(15) 33(2) 41(3) 55(3) 4(2) 5(2) -3(2)

C(16) 37(3) 69(4) 64(4) -4(3) 11(2) 0(3)

C(17) 40(3) 94(5) 78(5) 2(4) 20(3) 0(3)

C(18) 28(2) 67(4) 99(5) 7(4) 11(3) 1(2)

C(19) 34(3) 66(4) 96(5) -2(4) -7(3) -4(3)

C(20) 33(2) 59(3) 57(3) -8(3) -3(2) 3(2)

C(21) 38(2) 39(2) 35(2) -2(2) 3(2) 4(2)

C(22) 42(3) 47(3) 49(3) 2(2) 4(2) -1(2)

C(23) 52(3) 58(3) 33(3) 11(2) 3(2) 4(2)

C(24) 41(3) 82(4) 42(3) -3(3) -7(2) 2(3)

C(25) 39(3) 72(4) 51(3) -4(3) -5(2) -10(3)

C(26) 41(3) 52(3) 38(3) 0(2) 2(2) -6(2)

C(27) 46(3) 37(3) 60(3) 3(2) 8(2) 12(2)

C(28) 39(3) 57(4) 125(6) 15(4) 15(3) 6(3)

C(31) 27(2) 28(2) 37(2) 4(2) 2(2) 3(2)

C(32) 30(2) 34(2) 37(2) 2(2) -2(2) 4(2)

C(33) 36(2) 36(2) 38(2) 3(2) 5(2) 10(2)

C(34) 44(3) 33(2) 32(2) -1(2) 2(2) 9(2)

C(35) 36(2) 32(2) 38(2) -1(2) 3(2) 1(2)

C(36) 28(2) 30(2) 37(2) 3(2) 4(2) 2(2)

60


______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

C(37) 47(3) 42(3) 43(3) -10(2) -1(2) 0(2)

C(38) 44(3) 50(3) 44(3) -8(2) 1(2) 14(2)

C(41) 31(2) 21(2) 36(2) -4(2) -4(2) 0(2)

C(42) 33(2) 31(2) 40(3) 0(2) -2(2) 1(2)

C(43) 43(3) 29(2) 38(3) 2(2) -5(2) 2(2)

C(44) 54(3) 28(2) 35(2) 4(2) 0(2) -5(2)

C(45) 43(2) 29(2) 40(3) -5(2) 2(2) -9(2)

C(46) 34(2) 25(2) 37(2) 0(2) -5(2) -1(2)

C(47) 49(3) 38(3) 57(3) 1(2) 9(2) -10(2)

C(48) 58(3) 37(3) 39(3) 4(2) -8(2) 2(2)

C(51) 23(2) 26(2) 46(3) -4(2) -5(2) 5(2)

C(52) 29(2) 41(3) 46(3) -2(2) 0(2) 2(2)

C(53) 36(2) 43(3) 61(3) -11(2) -5(2) -4(2)

C(54) 32(2) 42(3) 68(4) -4(3) 0(2) -8(2)

C(55) 31(2) 36(2) 61(3) 1(2) 4(2) 1(2)

C(56) 30(2) 33(2) 46(3) 5(2) 1(2) 4(2)

C(57) 46(3) 54(3) 64(4) 5(3) 12(3) -9(3)

C(58) 57(4) 113(6) 68(5) -24(5) 0(3) -31(4)

C(61) 22(2) 24(2) 38(2) 1(2) -1(2) -2(2)

C(62) 23(2) 29(2) 36(2) 1(2) 2(2) 0(2)

C(63) 26(2) 35(2) 42(3) 3(2) 0(2) -1(2)

C(64) 29(2) 30(2) 49(3) 3(2) -3(2) 7(2)

C(65) 32(2) 33(2) 46(3) -4(2) -1(2) 6(2)

C(66) 31(2) 30(2) 36(2) -2(2) -4(2) 0(2)

C(67) 56(3) 58(4) 55(4) -12(3) -6(3) 27(3)

C(68) 43(3) 43(3) 41(3) 11(2) 0(2) 8(2)

B(1) 22(2) 27(2) 39(3) 2(2) -3(2) 3(2) ______________________________________________________________________________

61

Table 2.10. Bond lengths and angles for 2.26

______________________________________________________________________________________

Ru(1)-N(3) 2.057(4)

Ru(1)-C(5) 2.117(7)

Ru(1)-C(4) 2.122(7)

Ru(1)-C(1) 2.130(7)

Ru(1)-C(3) 2.153(6)

Ru(1)-C(2) 2.172(6)

Ru(1)-N(1) 2.212(4)

Ru(1)-P(1) 2.3306(12)

P(1)-C(13) 1.807(5)

P(1)-C(21) 1.836(5)

P(1)-C(15) 1.864(5)

F(31)-F(31') 0.84(9)

F(31)-C(37) 1.323(8)

F(31)-F(32') 1.65(8)

F(31')-C(37) 1.23(3)

F(31')-F(33) 1.53(9)

F(32)-F(32') 0.69(9)

F(32)-C(37) 1.340(9)

F(32)-F(33') 1.57(9)

F(32')-C(37) 1.27(4)

F(33)-F(33') 0.79(10)

F(33)-C(37) 1.308(8)

F(33')-C(37) 1.26(4)

F(34)-F(34') 1.007(17)

F(34)-F(35') 1.12(2)

F(34)-C(38) 1.243(9)

F(34')-C(38) 1.392(15)

F(34')-F(36) 1.49(2)

F(35)-F(36') 1.20(4)

F(35)-C(38) 1.319(8)

F(35)-F(35') 1.35(3)

F(35')-C(38) 1.331(15)

F(36)-F(36') 1.02(4)

F(36)-C(38) 1.327(9)

F(36')-C(38) 1.208(13)

F(41)-C(47) 1.322(7)

F(42)-C(47) 1.329(7)

F(43)-C(47) 1.316(7)

F(44)-C(48) 1.329(6)

F(45)-C(48) 1.299(7)

F(46)-C(48) 1.325(6)

F(51)-F(51') 0.85(4)

F(51)-C(57) 1.280(10)

F(51)-F(52') 1.37(4)

F(51')-C(57) 1.32(2)

F(51')-F(53) 1.64(5)

F(52)-F(52') 1.00(5)

F(52)-C(57) 1.324(10)

F(52)-F(53') 1.62(5)

F(52')-C(57) 1.280(19)

F(53)-F(53') 0.64(7)

F(53)-C(57) 1.294(15)

F(53')-C(57) 1.29(3)

F(54)-C(58) 1.428(11)

F(54)-F(54') 1.61(3)

F(54')-F(55) 0.57(3)

F(54')-C(58) 1.16(2)

F(55)-C(58) 1.261(12)

F(55)-F(55') 1.597(19)

F(55')-F(56) 1.64(2)

F(55')-C(58) 1.781(17)

F(56)-C(58) 1.233(16)

62

Table 2.10. Continued ___________________________________________________________________________________

F(56')-C(58) 1.37(3)

F(61)-C(67) 1.298(14)

F(61')-C(67) 1.30(4)

F(62)-C(67) 1.282(14)

F(62')-C(67) 1.33(4)

F(63)-C(67) 1.348(14)

F(63')-C(67) 1.30(3)

F(64)-F(65') 1.11(4)

F(64)-F(64') 1.13(4)

F(64)-C(68) 1.289(7)

F(64')-C(68) 1.315(17)

F(64')-F(66) 1.33(4)

F(65)-F(66') 1.17(4)

F(65)-C(68) 1.321(8)

F(65)-F(65') 1.33(4)

F(65')-C(68) 1.303(18)

F(66)-F(66') 1.10(5)

F(66)-C(68) 1.331(8)

F(66')-C(68) 1.219(18)

N(1)-C(13) 1.316(6)

N(1)-C(11) 1.389(6)

N(2)-C(13) 1.349(6)

N(2)-C(12) 1.376(7)

N(2)-C(14) 1.465(6)

N(3)-C(27) 1.134(7)

C(1)-C(5) 1.366(16)

C(1)-C(2) 1.369(13)

C(2)-C(3) 1.356(13)

C(3)-C(4) 1.339(16)

C(4)-C(5) 1.363(18)

C(7)-C(10) 1.509(9)

C(7)-C(11) 1.513(8)

C(7)-C(8) 1.522(8)

C(7)-C(9) 1.535(9)

C(11)-C(12) 1.359(7)

C(15)-C(16) 1.510(8)

C(15)-C(20) 1.540(7)

C(16)-C(17) 1.546(7)

C(17)-C(18) 1.498(10)

C(18)-C(19) 1.519(10)

C(19)-C(20) 1.539(7)

C(21)-C(26) 1.515(7)

C(21)-C(22) 1.555(7)

C(22)-C(23) 1.509(8)

C(23)-C(24) 1.531(8)

C(24)-C(25) 1.512(9)

C(25)-C(26) 1.543(7)

C(27)-C(28) 1.462(8)

C(31)-C(36) 1.401(6)

C(31)-C(32) 1.405(6)

C(31)-B(1) 1.630(7)

C(32)-C(33) 1.381(7)

C(33)-C(34) 1.376(7)

C(33)-C(38) 1.501(6)

C(34)-C(35) 1.393(6)

C(35)-C(36) 1.379(6)

C(35)-C(37) 1.511(7)

C(41)-C(46) 1.403(6)

C(41)-C(42) 1.408(6)

C(41)-B(1) 1.624(7)

C(42)-C(43) 1.374(7)

C(43)-C(44) 1.389(7)

C(43)-C(48) 1.525(7)

C(44)-C(45) 1.383(7)

63

Table 2.10. Continued ________________________________________________________________________________

C(45)-C(46) 1.387(7)

C(45)-C(47) 1.497(7)

C(51)-C(52) 1.386(7)

C(51)-C(56) 1.405(7)

C(51)-B(1) 1.643(6)

C(52)-C(53) 1.406(7)

C(53)-C(54) 1.375(8)

C(53)-C(58) 1.494(9)

C(54)-C(55) 1.379(8)

C(55)-C(56) 1.388(7)

C(55)-C(57) 1.512(8)

C(61)-C(62) 1.380(6)

C(61)-C(66) 1.406(6)

C(61)-B(1) 1.645(6)

C(62)-C(63) 1.394(6)

C(63)-C(64) 1.378(7)

C(63)-C(68) 1.489(7)

C(64)-C(65) 1.382(7)

C(65)-C(66) 1.385(6)

C(65)-C(67) 1.504(7)

N(3)-Ru(1)-C(5) 142.3(6)

N(3)-Ru(1)-C(4) 105.3(5)

C(5)-Ru(1)-C(4) 37.5(5)

N(3)-Ru(1)-C(1) 149.9(3)

C(5)-Ru(1)-C(1) 37.5(5)

C(4)-Ru(1)-C(1) 62.4(4)

N(3)-Ru(1)-C(3) 92.0(2)

C(5)-Ru(1)-C(3) 61.5(4)

C(4)-Ru(1)-C(3) 36.5(4)

C(1)-Ru(1)-C(3) 61.4(3)

N(3)-Ru(1)-C(2) 113.0(3)

C(5)-Ru(1)-C(2) 62.1(3)

C(4)-Ru(1)-C(2) 61.7(3)

C(1)-Ru(1)-C(2) 37.1(4)

C(3)-Ru(1)-C(2) 36.5(4)

N(3)-Ru(1)-N(1) 80.73(15)

C(5)-Ru(1)-N(1) 137.0(6)

C(4)-Ru(1)-N(1) 171.4(3)

C(1)-Ru(1)-N(1) 109.3(3)

C(3)-Ru(1)-N(1) 138.8(4)

C(2)-Ru(1)-N(1) 110.5(2)

N(3)-Ru(1)-P(1) 95.41(12)

C(5)-Ru(1)-P(1) 99.2(2)

C(4)-Ru(1)-P(1) 118.0(4)

C(1)-Ru(1)-P(1) 114.6(3)

C(3)-Ru(1)-P(1) 154.4(4)

C(2)-Ru(1)-P(1) 151.0(3)

N(1)-Ru(1)-P(1) 66.75(10)

C(13)-P(1)-C(21) 111.7(2)

C(13)-P(1)-C(15) 105.0(2)

C(21)-P(1)-C(15) 106.3(2)

C(13)-P(1)-Ru(1) 84.09(15)

C(21)-P(1)-Ru(1) 128.35(16)

C(15)-P(1)-Ru(1) 116.70(17)

F(31')-F(31)-C(37) 65(3)

F(31')-F(31)-F(32') 111(4)

C(37)-F(31)-F(32') 49(2)

F(31)-F(31')-C(37) 77(3)

F(31)-F(31')-F(33) 123(4)

C(37)-F(31')-F(33) 55(3)

F(32')-F(32)-C(37) 69(4)

F(32')-F(32)-F(33') 117(5)

64

Table 2.10. Continued ___________________________________________________________________________________

C(37)-F(32)-F(33') 50(2)

F(32)-F(32')-C(37) 80(5)

F(32)-F(32')-F(31) 125(5)

C(37)-F(32')-F(31) 52(3)

F(33')-F(33)-C(37) 69(4)

F(33')-F(33)-F(31') 117(4)

C(37)-F(33)-F(31') 51(2)

F(33)-F(33')-C(37) 76(4)

F(33)-F(33')-F(32) 122(5)

C(37)-F(33')-F(32) 55(3)

F(34')-F(34)-F(35') 136(2)

F(34')-F(34)-C(38) 75.6(11)

F(35')-F(34)-C(38) 68.3(12)

F(34)-F(34')-C(38) 59.9(9)

F(34)-F(34')-F(36) 111.5(14)

C(38)-F(34')-F(36) 54.6(8)

F(36')-F(35)-C(38) 57.2(9)

F(36')-F(35)-F(35') 107.8(12)

C(38)-F(35)-F(35') 59.7(8)

F(34)-F(35')-C(38) 60.2(7)

F(34)-F(35')-F(35) 114.6(14)

C(38)-F(35')-F(35) 58.8(11)

F(36')-F(36)-C(38) 60.2(12)

F(36')-F(36)-F(34') 108.0(15)

C(38)-F(36)-F(34') 58.8(8)

F(36)-F(36')-F(35) 137.9(15)

F(36)-F(36')-C(38) 72.5(13)

F(35)-F(36')-C(38) 66.6(14)

F(51')-F(51)-C(57) 74(2)

F(51')-F(51)-F(52') 129(3)

C(57)-F(51)-F(52') 57.6(13)

F(51)-F(51')-C(57) 68.1(17)

F(51)-F(51')-F(53) 111(3)

C(57)-F(51')-F(53) 50.4(15)

F(52')-F(52)-C(57) 65.2(14)

F(52')-F(52)-F(53') 107(2)

C(57)-F(52)-F(53') 50.7(16)

F(52)-F(52')-C(57) 70(2)

F(52)-F(52')-F(51) 123(2)

C(57)-F(52')-F(51) 57.5(12)

F(53')-F(53)-C(57) 75(4)

F(53')-F(53)-F(51') 118(4)

C(57)-F(53)-F(51') 52.0(14)

F(53)-F(53')-C(57) 76(4)

F(53)-F(53')-F(52) 128(5)

C(57)-F(53')-F(52) 52.8(17)

C(58)-F(54)-F(54') 44.5(7)

F(55)-F(54')-C(58) 86(3)

F(55)-F(54')-F(54) 146(3)

C(58)-F(54')-F(54) 59.6(14)

F(54')-F(55)-C(58) 67(3)

F(54')-F(55)-F(55') 130(4)

C(58)-F(55)-F(55') 76.1(9)

F(55)-F(55')-F(56) 79.6(9)

F(55)-F(55')-C(58) 43.4(5)

F(56)-F(55')-C(58) 42.0(6)

C(58)-F(56)-F(55') 75.1(12)

F(65')-F(64)-F(64') 127(2)

F(65')-F(64)-C(68) 65.3(13)

F(64')-F(64)-C(68) 65.4(14)

F(64)-F(64')-C(68) 63.1(10)

F(64)-F(64')-F(66) 117.3(15)

C(68)-F(64')-F(66) 60.5(13)

F(66')-F(65)-C(68) 58.3(12)

65

Table 2.10. Continued ___________________________________________________________________________________

F(66')-F(65)-F(65') 108.1(17)

C(68)-F(65)-F(65') 58.8(12)

F(64)-F(65')-C(68) 63.9(13)

F(64)-F(65')-F(65) 119.0(17)

C(68)-F(65')-F(65) 60.2(12)

F(66')-F(66)-F(64') 111.1(16)

F(66')-F(66)-C(68) 59.4(13)

F(64')-F(66)-C(68) 59.3(10)

F(66)-F(66')-F(65) 135.5(18)

F(66)-F(66')-C(68) 69.9(18)

F(65)-F(66')-C(68) 67.2(16)

C(13)-N(1)-C(11) 107.8(4)

C(13)-N(1)-Ru(1) 101.9(3)

C(11)-N(1)-Ru(1) 149.3(3)

C(13)-N(2)-C(12) 106.0(4)

C(13)-N(2)-C(14) 126.9(4)

C(12)-N(2)-C(14) 127.1(4)

C(27)-N(3)-Ru(1) 169.4(5)

C(5)-C(1)-C(2) 108.1(9)

C(5)-C(1)-Ru(1) 70.7(5)

C(2)-C(1)-Ru(1) 73.1(4)

C(3)-C(2)-C(1) 106.8(9)

C(3)-C(2)-Ru(1) 71.0(4)

C(1)-C(2)-Ru(1) 69.8(4)

C(4)-C(3)-C(2) 109.6(9)

C(4)-C(3)-Ru(1) 70.5(5)

C(2)-C(3)-Ru(1) 72.5(4)

C(3)-C(4)-C(5) 107.9(9)

C(3)-C(4)-Ru(1) 73.0(5)

C(5)-C(4)-Ru(1) 71.1(5)

C(4)-C(5)-C(1) 107.6(8)

C(4)-C(5)-Ru(1) 71.4(5)

C(1)-C(5)-Ru(1) 71.7(4)

C(10)-C(7)-C(11) 110.6(5)

C(10)-C(7)-C(8) 108.5(5)

C(11)-C(7)-C(8) 109.7(5)

C(10)-C(7)-C(9) 110.7(6)

C(11)-C(7)-C(9) 107.5(5)

C(8)-C(7)-C(9) 110.0(5)

C(12)-C(11)-N(1) 106.4(4)

C(12)-C(11)-C(7) 130.2(5)

N(1)-C(11)-C(7) 123.4(4)

C(11)-C(12)-N(2) 108.8(4)

N(1)-C(13)-N(2) 111.0(4)

N(1)-C(13)-P(1) 105.3(3)

N(2)-C(13)-P(1) 143.3(4)

C(16)-C(15)-C(20) 110.7(4)

C(16)-C(15)-P(1) 115.3(4)

C(20)-C(15)-P(1) 109.3(4)

C(15)-C(16)-C(17) 109.6(5)

C(18)-C(17)-C(16) 112.9(6)

C(17)-C(18)-C(19) 110.6(5)

C(18)-C(19)-C(20) 110.3(5)

C(19)-C(20)-C(15) 109.5(5)

C(26)-C(21)-C(22) 109.9(4)

C(26)-C(21)-P(1) 112.8(3)

C(22)-C(21)-P(1) 108.0(3)

C(23)-C(22)-C(21) 111.0(4)

C(22)-C(23)-C(24) 111.3(4)

C(25)-C(24)-C(23) 111.3(5)

C(24)-C(25)-C(26) 111.0(5)

C(21)-C(26)-C(25) 110.5(4)

N(3)-C(27)-C(28) 178.0(7)

C(36)-C(31)-C(32) 115.1(4)

66

Table 2.10. Continued ___________________________________________________________________________________

C(36)-C(31)-B(1) 123.0(4)

C(32)-C(31)-B(1) 121.1(4)

C(33)-C(32)-C(31) 122.3(4)

C(34)-C(33)-C(32) 121.6(4)

C(34)-C(33)-C(38) 119.3(4)

C(32)-C(33)-C(38) 119.1(4)

C(33)-C(34)-C(35) 117.4(4)

C(36)-C(35)-C(34) 121.1(4)

C(36)-C(35)-C(37) 120.9(4)

C(34)-C(35)-C(37) 117.9(4)

C(35)-C(36)-C(31) 122.5(4)

F(31')-C(37)-F(33') 108(4)

F(31')-C(37)-F(32') 114(3)

F(33')-C(37)-F(32') 103(3)

F(31')-C(37)-F(33) 74(5)

F(33')-C(37)-F(33) 36(5)

F(32')-C(37)-F(33) 127(3)

F(31')-C(37)-F(31) 38(5)

F(33')-C(37)-F(31) 133(3)

F(32')-C(37)-F(31) 79(4)

F(33)-C(37)-F(31) 106.8(6)

F(31')-C(37)-F(32) 134(2)

F(33')-C(37)-F(32) 74(5)

F(32')-C(37)-F(32) 31(4)

F(33)-C(37)-F(32) 104.6(6)

F(31)-C(37)-F(32) 105.9(6)

F(31')-C(37)-C(35) 109.5(16)

F(33')-C(37)-C(35) 110(2)

F(32')-C(37)-C(35) 111(2)

F(33)-C(37)-C(35) 113.7(5)

F(31)-C(37)-C(35) 112.8(5)

F(32)-C(37)-C(35) 112.4(6)

F(36')-C(38)-F(34) 127.3(9)

F(36')-C(38)-F(35) 56.3(18)

F(34)-C(38)-F(35) 109.1(8)

F(36')-C(38)-F(36) 47.3(18)

F(34)-C(38)-F(36) 108.5(9)

F(35)-C(38)-F(36) 103.1(7)

F(36')-C(38)-F(35') 108.6(16)

F(34)-C(38)-F(35') 51.5(13)

F(35)-C(38)-F(35') 61.4(14)

F(36)-C(38)-F(35') 135.8(7)

F(36')-C(38)-F(34') 104.3(15)

F(34)-C(38)-F(34') 44.5(8)

F(35)-C(38)-F(34') 132.7(7)

F(36)-C(38)-F(34') 66.6(11)

F(35')-C(38)-F(34') 93.1(13)

F(36')-C(38)-C(33) 119.1(9)

F(34)-C(38)-C(33) 113.1(5)

F(35)-C(38)-C(33) 112.7(5)

F(36)-C(38)-C(33) 109.9(5)

F(35')-C(38)-C(33) 114.2(7)

F(34')-C(38)-C(33) 114.2(7)

C(46)-C(41)-C(42) 115.5(4)

C(46)-C(41)-B(1) 123.3(4)

C(42)-C(41)-B(1) 120.7(4)

C(43)-C(42)-C(41) 122.7(4)

C(42)-C(43)-C(44) 120.4(4)

C(42)-C(43)-C(48) 117.5(4)

C(44)-C(43)-C(48) 122.0(4)

C(45)-C(44)-C(43) 118.6(4)

C(44)-C(45)-C(46) 120.8(4)

C(44)-C(45)-C(47) 121.3(4)

C(46)-C(45)-C(47) 117.9(4)

67

Table 2.10. Continued ___________________________________________________________________________________

C(45)-C(46)-C(41) 122.0(4)

F(43)-C(47)-F(41) 105.2(5)

F(43)-C(47)-F(42) 105.6(5)

F(41)-C(47)-F(42) 107.8(5)

F(43)-C(47)-C(45) 113.0(4)

F(41)-C(47)-C(45) 112.3(5)

F(42)-C(47)-C(45) 112.4(5)

F(45)-C(48)-F(46) 107.5(4)

F(45)-C(48)-F(44) 107.7(5)

F(46)-C(48)-F(44) 106.3(5)

F(45)-C(48)-C(43) 112.9(4)

F(46)-C(48)-C(43) 111.7(5)

F(44)-C(48)-C(43) 110.3(4)

C(52)-C(51)-C(56) 116.2(4)

C(52)-C(51)-B(1) 122.1(4)

C(56)-C(51)-B(1) 121.4(4)

C(51)-C(52)-C(53) 122.1(5)

C(54)-C(53)-C(52) 120.3(5)

C(54)-C(53)-C(58) 118.8(5)

C(52)-C(53)-C(58) 120.9(6)

C(53)-C(54)-C(55) 118.8(5)

C(54)-C(55)-C(56) 120.9(5)

C(54)-C(55)-C(57) 119.3(5)

C(56)-C(55)-C(57) 119.7(5)

C(55)-C(56)-C(51) 121.7(5)

F(51)-C(57)-F(52') 65(2)

F(51)-C(57)-F(53') 123.9(16)

F(52')-C(57)-F(53') 112(2)

F(51)-C(57)-F(53) 109.6(11)

F(52')-C(57)-F(53) 132.9(17)

F(53')-C(57)-F(53) 29(3)

F(51)-C(57)-F(51') 38.0(19)

F(52')-C(57)-F(51') 101.6(17)

F(53')-C(57)-F(51') 102(2)

F(53)-C(57)-F(51') 78(2)

F(51)-C(57)-F(52) 107.1(8)

F(52')-C(57)-F(52) 45(2)

F(53')-C(57)-F(52) 76(3)

F(53)-C(57)-F(52) 104.7(9)

F(51')-C(57)-F(52) 136.6(13)

F(51)-C(57)-C(55) 113.5(7)

F(52')-C(57)-C(55) 113.6(11)

F(53')-C(57)-C(55) 117.1(14)

F(53)-C(57)-C(55) 111.0(7)

F(51')-C(57)-C(55) 108.5(12)

F(52)-C(57)-C(55) 110.6(6)

F(54')-C(58)-F(56) 118.1(15)

F(54')-C(58)-F(55) 27.0(16)

F(56)-C(58)-F(55) 112.4(13)

F(54')-C(58)-F(56') 119.5(19)

F(56)-C(58)-F(56') 15.3(19)

F(55)-C(58)-F(56') 121.4(15)

F(54')-C(58)-F(54) 75.9(16)

F(56)-C(58)-F(54) 106.3(11)

F(55)-C(58)-F(54) 102.8(8)

F(56')-C(58)-F(54) 91.5(14)

F(54')-C(58)-C(53) 123.7(15)

F(56)-C(58)-C(53) 114.0(9)

F(55)-C(58)-C(53) 112.0(8)

F(56')-C(58)-C(53) 116.4(14)

F(54)-C(58)-C(53) 108.5(7)

F(54')-C(58)-F(55') 83.4(14)

F(56)-C(58)-F(55') 62.9(12)

F(55)-C(58)-F(55') 60.5(9)

68

Table 2.10. Continued ___________________________________________________________________________________

F(56')-C(58)-F(55') 77.7(13)

F(54)-C(58)-F(55') 148.1(7)

C(53)-C(58)-F(55') 103.2(7)

C(62)-C(61)-C(66) 116.1(4)

C(62)-C(61)-B(1) 123.0(4)

C(66)-C(61)-B(1) 120.6(4)

C(61)-C(62)-C(63) 122.4(4)

C(64)-C(63)-C(62) 120.6(4)

C(64)-C(63)-C(68) 120.1(4)

C(62)-C(63)-C(68) 119.3(4)

C(63)-C(64)-C(65) 118.3(4)

C(64)-C(65)-C(66) 121.0(4)

C(64)-C(65)-C(67) 118.5(4)

C(66)-C(65)-C(67) 120.5(5)

C(65)-C(66)-C(61) 121.7(4)

F(62)-C(67)-F(61') 118(2)

F(62)-C(67)-F(63') 10(3)

F(61')-C(67)-F(63') 111(3)

F(62)-C(67)-F(61) 109.9(13)

F(61')-C(67)-F(61) 87(3)

F(63')-C(67)-F(61) 117.2(19)

F(62)-C(67)-F(62') 95(3)

F(61')-C(67)-F(62') 106(3)

F(63')-C(67)-F(62') 104(3)

F(61)-C(67)-F(62') 20(4)

F(62)-C(67)-F(63) 103.2(11)

F(61')-C(67)-F(63) 19(3)

F(63')-C(67)-F(63) 95(2)

F(61)-C(67)-F(63) 103.3(10)

F(62')-C(67)-F(63) 120(3)

F(62)-C(67)-C(65) 113.6(8)

F(61')-C(67)-C(65) 110.7(19)

F(63')-C(67)-C(65) 113.1(17)

F(61)-C(67)-C(65) 114.4(7)

F(62')-C(67)-C(65) 111.8(15)

F(63)-C(67)-C(65) 111.3(8)

F(66')-C(68)-F(64) 126.6(10)

F(66')-C(68)-F(65') 107(2)

F(64)-C(68)-F(65') 50.8(19)

F(66')-C(68)-F(64') 104(2)

F(64)-C(68)-F(64') 51.4(18)

F(65')-C(68)-F(64') 100(2)

F(66')-C(68)-F(65) 55(2)

F(64)-C(68)-F(65) 107.8(7)

F(65')-C(68)-F(65) 61.0(19)

F(64')-C(68)-F(65) 137.5(9)

F(66')-C(68)-F(66) 51(2)

F(64)-C(68)-F(66) 106.7(7)

F(65')-C(68)-F(66) 134.9(11)

F(64')-C(68)-F(66) 60.3(18)

F(65)-C(68)-F(66) 104.4(8)

F(66')-C(68)-C(63) 118.8(9)

F(64)-C(68)-C(63) 114.5(5)

F(65')-C(68)-C(63) 113.1(10)

F(64')-C(68)-C(63) 111.6(9)

F(65)-C(68)-C(63) 110.8(5)

F(66)-C(68)-C(63) 112.0(5)

C(41)-B(1)-C(31) 102.5(3)

C(41)-B(1)-C(51) 111.8(4)

C(31)-B(1)-C(51) 113.2(4)

C(41)-B(1)-C(61) 112.5(4)

C(31)-B(1)-C(61) 113.4(4)

C(51)-B(1)-C(61) 103.7(3)

69

Figure 2.22. Synthesis of 2.20

Synthesis of [CpRu (4-(tert-butyl)-2-(di-tert-butylphosphino)-1-methyl-1H-

imidazole)(acetonitrile)]PF6 (2.20) In a glove box, ruthenium precursor


equipped with a magnetic stir bar and deoxygenated acetone (4 mL). The phosphine 4-

(tert-butyl)-2-(di-tert-butylphosphino)-1-methyl-1H-imidazole, (70.7 mg, 0.250 mmol)

was added dropwise in deoxygenated acetone (3 mL), and the resulting solution was

allowed to stir overnight at room temperature under an atmosphere of nitrogen. The

solvent was removed in vacuo, without stirring, and the residue left under vacuum until a

flaky powder. The product was obtained as yellow colored powder in 101.6 % yield

(161.1 mg, ~4 mol% acetone is present). 1H NMR (500 MHz, acetone-d6) δ 1.41 (s, 9 H),

1.46 (broad d, J = 14.5, 18H), 2.44 (s, 3 H), 3.86 (s, 3 H), 4.58 (s, 5 H), 7.05 (s, 1 H)

ppm. 31P NMR (202 MHz, acetone-d6) δ 58.59 (s) ppm. Elemental calculated for

C23H39F6N3P2Ru (634.58) C, 43.53; H, 6.19; N, 6.62. Found C, 42.66; H, 5.94; N, 6.33.

70

Figure 2.23. Anion exchange of 2.20

Synthesis of [CpRu (4-(tert-butyl)-2-(di-tert-butylphosphino)-1-methyl-1H-

imidazole)(acetonitrile)]B[(C6F5)]4 (2.27) In a glove box, ruthenium complex 2.20

(63.5 mg, 0.100 mmol) was combined in a scintillation vial equipped with a magnetic stir

bar and deoxygenated ethyl ether (2 mL). The salt, potassium

tetrakis(pentafluorophenyl)borate, (71.8 mg, 0.100 mmol) was added dropwise in

deoxygenated ethyl ether (3 mL), and the resulting solution was allowed to stir overnight

at room temperature under an atmosphere of nitrogen. Deoxygenated water (4 mL) was

added to dissolve potassium hexafluorophosphate and excess potassium

tetrakis(pentafluorophenyl)borate, and the mixture was allowed to stir for 3 h. The

organic layer was separated and aqueous layer was washed with ethyl ether (2 x 2 mL).

The solvent was removed from combined organic layers in vacuo, without stirring, and

the residue left under vacuum until a flaky powder remained. The product was obtained

as a yellow colored powder in 95.2 % yield (111.3 mg, ethyl ether present). Single

crystals were obtained from pentane diffusion into THF solution of 2.27 at room

temperature. X-ray analysis of crystals revealed the structure. 1H NMR (400 MHz,

acetone-d6) δ 1.41 (s, 9 H), 1.46 (broad d, J = 14.5, 18H), 2.44 (s, 3 H), 3.86 (s, 3 H),

4.58 (s, 5 H), 7.05 (s, 1 H) ppm. 31P NMR (162 MHz, acetone-d6) δ 58.58 (s) ppm. 19F

71

NMR (376 MHz, acetone-d6) δ -133.04 (s), -164.52 (t, J = 20), -168.45 (t, J = 17.5) ppm.

Table 2.11. Crystal data and structure refinement for 2.27

Empirical formula C47 H39 B F20 N3 P Ru

Formula weight 1168.66

Temperature 100(2) K

Wavelength 1.54184 Å

Crystal system Triclinic

Space group P1

Unit cell dimensions

a = 13.4597(10) Å α = 65.352(2)° b = 13.7879(7) Å β = 66.222(3)° c = 16.0133(11) Å γ = 62.597(2)°

Volume 2314.3(3) Å3

Z 2

Density (calculated) 1.677 Mg/m3

Absorption coefficient 4.161 mm-1

F(000) 1172

Crystal size 0.25 x 0.25 x 0.15 mm3

Crystal color, habit Orange block

Theta range for data collection

3.15 to 65.90°

Index ranges -15<=h<=15, -16<=k<=16, -

18<=l<=18

Reflections collected 11493

Independent reflections 11493 [R(int) = 0.0491]

72


Completeness to theta = 65.00° 99.0 %

Absorption correction Multi-scan

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 11493 / 3 / 1370

Goodness-of-fit on F2 1.046

Final R indices [I>2sigma(I)] R1 = 0.0277, wR2 = 0.0694

R indices (all data) R1 = 0.0278, wR2 = 0.0695

Largest diff. peak and hole 0.640 and -0.788 e.Å-3

Absolute structure parameter 0.002(4)

Table 2.12. Atomic coordinates (x 104) and equivalent isotropic displacement parameters (Å2x 103) for 2.27. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor ________________________________________________________________________________

x y z U(eq) ________________________________________________________________________________

Ru(1) 3382(1) 6724(1) 2305(1) 18(1)

Ru(1') 6665(1) 3332(1) 7329(1) 17(1)

P(1) 1681(1) 8392(1) 2538(1) 17(1)

P(1') 8274(1) 1624(1) 7686(1) 17(1)

N(1) 3753(3) 8049(3) 2397(2) 20(1)

N(2) 2864(3) 9733(3) 2640(2) 19(1)

N(3) 3366(3) 6020(3) 3721(3) 23(1)

N(1') 8129(3) 3659(3) 7299(2) 18(1)

73


________________________________________________________________________________

x y z U(eq) ________________________________________________________________________________

N(2') 9754(3) 2685(3) 7750(2) 19(1)

N(3') 6055(3) 3453(3) 8696(3) 23(1)

B(1) 4560(4) 964(4) 4853(4) 20(1)

B(1') 946(4) 4706(4) 9814(4) 18(1)

F(1) 6059(2) 413(2) 2962(2) 27(1)

F(2) 7451(2) 1478(2) 1631(2) 36(1)

F(3) 7838(2) 3075(3) 1924(2) 42(1)

F(4) 6737(2) 3586(2) 3617(2) 36(1)

F(5) 5297(2) 2549(2) 4961(2) 26(1)

F(6) 3729(2) 1873(2) 3196(2) 23(1)

F(7) 1995(2) 3761(2) 2723(2) 27(1)

F(8) 794(2) 5203(2) 3844(2) 29(1)

F(9) 1305(2) 4592(2) 5520(2) 25(1)

F(10) 2927(2) 2638(2) 6068(2) 21(1)

F(11) 6413(2) -1175(2) 4751(2) 27(1)

F(12) 6287(3) -3074(2) 4799(2) 41(1)

F(13) 4258(2) -3102(2) 4854(2) 36(1)

F(14) 2362(2) -1166(2) 4808(2) 28(1)

F(15) 2435(2) 711(2) 4788(2) 24(1)

F(16) 2751(2) 492(2) 6519(2) 22(1)

F(17) 2891(2) -654(2) 8296(2) 29(1)

F(18) 4909(2) -1383(2) 8762(2) 32(1)

F(19) 6769(2) -906(2) 7391(2) 32(1)

F(20) 6660(2) 224(2) 5613(2) 28(1)

F(1') 1700(2) 3784(2) 8228(2) 25(1)

F(2') 3407(2) 1888(2) 7929(2) 34(1)

F(3') 4799(2) 565(2) 9135(2) 43(1)

F(4') 4405(2) 1216(2) 10672(2) 35(1)

F(5') 2636(2) 3033(2) 11043(2) 23(1)

F(6') -953(2) 6823(2) 9430(2) 23(1)

74


________________________________________________________________________________

x y z U(eq) ________________________________________________________________________________

F(7') -2975(2) 7144(2) 9251(2) 30(1)

F(8') -3481(2) 5329(2) 9477(2) 33(1)

F(9') -1842(2) 3213(2) 9765(2) 30(1)

F(10') 205(2) 2879(2) 9849(2) 24(1)

F(11') 346(2) 2959(2) 11476(2) 22(1)

F(12') -657(2) 3040(2) 13260(2) 32(1)

F(13') -1203(2) 4950(2) 13725(2) 36(1)

F(14') -621(2) 6748(2) 12336(2) 32(1)

F(15') 385(2) 6687(2) 10558(2) 26(1)

F(16') 2650(2) 5219(2) 10060(2) 26(1)

F(17') 3846(2) 6556(2) 8806(2) 36(1)

F(18') 3480(2) 7715(2) 7038(2) 37(1)

F(19') 1891(2) 7462(2) 6567(2) 33(1)

F(20') 667(2) 6172(2) 7807(2) 26(1)

C(1) 4503(4) 6505(4) 907(3) 28(1)

C(2) 3367(4) 6622(4) 985(3) 30(1)

C(3) 3068(4) 5730(4) 1744(3) 31(1)

C(4) 4017(4) 5036(3) 2159(3) 29(1)

C(5) 4920(4) 5511(3) 1642(3) 28(1)

C(6) 2732(3) 8855(3) 2576(3) 19(1)

C(7) 4033(3) 9430(3) 2516(3) 21(1)

C(8) 4589(3) 8396(3) 2361(3) 23(1)

C(9) 5894(4) 7744(4) 2113(4) 31(1)

C(10) 6184(4) 6523(4) 2790(4) 35(1)

C(11) 6518(4) 8376(4) 2189(4) 35(1)

C(12) 6278(4) 7684(5) 1096(4) 43(1)

C(13) 2006(4) 10815(3) 2803(3) 23(1)

C(14) 1177(4) 9389(3) 1428(3) 25(1)

C(15) 697(4) 8788(4) 1137(3) 30(1)

75


________________________________________________________________________________

x y z U(eq) ________________________________________________________________________________

C(16) 230(4) 10547(3) 1528(4) 32(1)

C(17) 2258(4) 9604(4) 656(3) 33(1)

C(18) 420(3) 8496(3) 3625(3) 22(1)

C(19) 847(4) 7533(3) 4469(3) 27(1)

C(20) -517(4) 8281(4) 3490(3) 31(1)

C(21) -86(4) 9611(3) 3889(3) 28(1)

C(22) 3463(3) 5535(3) 4477(3) 22(1)

C(23) 3549(4) 4961(3) 5458(3) 30(1)

C(24) 5619(3) 1397(3) 4049(3) 20(1)

C(25) 6200(3) 1177(3) 3183(3) 22(1)

C(26) 6948(3) 1724(4) 2466(3) 25(1)

C(27) 7134(4) 2524(4) 2612(3) 28(1)

C(28) 6574(4) 2791(3) 3470(3) 26(1)

C(29) 5847(3) 2225(3) 4152(3) 19(1)

C(30) 3428(3) 2127(3) 4665(3) 19(1)

C(31) 3131(3) 2505(3) 3804(3) 21(1)

C(32) 2247(3) 3490(3) 3544(3) 20(1)

C(33) 1620(4) 4211(3) 4109(3) 21(1)

C(34) 1884(3) 3897(3) 4962(3) 21(1)

C(35) 2758(3) 2878(3) 5214(3) 18(1)

C(36) 4442(3) -114(3) 4752(3) 18(1)

C(37) 5391(4) -1132(3) 4760(3) 22(1)

C(38) 5343(4) -2121(3) 4796(3) 27(1)

C(39) 4312(4) -2141(3) 4824(3) 28(1)

C(40) 3363(4) -1171(3) 4805(3) 22(1)

C(41) 3442(3) -193(3) 4777(3) 20(1)

C(42) 4678(3) 445(3) 5959(3) 19(1)

C(43) 5686(3) 50(3) 6243(3) 21(1)

C(44) 5761(4) -549(3) 7175(3) 24(1)

76


________________________________________________________________________________

x y z U(eq) ________________________________________________________________________________

C(45) 4838(4) -800(3) 7863(3) 24(1)

C(46) 3823(3) -430(3) 7631(3) 22(1)

C(47) 3774(3) 167(3) 6702(3) 21(1)

C(1') 6325(4) 4366(4) 5936(3) 32(1)

C(2') 5363(4) 4789(3) 6664(3) 26(1)

C(3') 4928(3) 3901(4) 7248(3) 29(1)

C(4') 5592(4) 2934(4) 6903(4) 33(1)

C(5') 6467(4) 3232(4) 6084(4) 35(1)

C(6') 8842(3) 2612(3) 7645(3) 18(1)

C(7') 9579(3) 3823(3) 7477(3) 19(1)

C(8') 8581(3) 4432(3) 7185(3) 17(1)

C(9') 8104(3) 5701(3) 6716(3) 22(1)

C(10') 6786(4) 6200(3) 7130(3) 28(1)

C(11') 8711(4) 6312(3) 6844(3) 26(1)

C(12') 8354(4) 5878(4) 5654(3) 27(1)

C(13') 10723(3) 1778(3) 8116(3) 23(1)

C(14') 9290(3) 1008(3) 6658(3) 24(1)

C(15') 8663(5) 471(6) 6457(5) 58(2)

C(16') 10456(4) 108(4) 6822(4) 37(1)

C(17') 9534(4) 1990(4) 5810(3) 39(1)

C(18') 8214(4) 481(3) 8854(3) 23(1)

C(19A) 9219(8) -674(8) 8991(7) 31(2)

C(20A) 8125(7) 986(6) 9636(6) 24(2)

C(21A) 7076(8) 308(7) 9140(7) 30(2)

C(19B) 9308(8) -144(9) 9162(8) 39(2)

C(20B) 7237(8) 985(7) 9590(7) 33(2)

C(21B) 7887(7) -378(7) 8691(7) 28(2)

C(22') 5631(3) 3580(3) 9437(3) 24(1)

C(23') 5153(4) 3666(4) 10404(3) 30(1)

77


________________________________________________________________________________

x y z U(eq) ________________________________________________________________________________

C(24') 2026(3) 3495(3) 9673(3) 19(1)

C(25') 2314(3) 3155(3) 8892(3) 20(1)

C(26') 3222(4) 2173(3) 8697(3) 25(1)

C(27') 3929(4) 1508(3) 9306(3) 27(1)

C(28') 3715(3) 1835(3) 10072(3) 25(1)

C(29') 2781(3) 2803(3) 10258(3) 20(1)

C(30') -240(3) 4847(3) 9624(3) 19(1)

C(31') -1128(3) 5898(3) 9501(3) 19(1)

C(32') -2188(3) 6080(4) 9431(3) 25(1)

C(33') -2438(3) 5181(4) 9528(3) 24(1)

C(34') -1613(4) 4105(4) 9677(3) 24(1)

C(35') -542(3) 3968(3) 9715(3) 21(1)

C(36') 450(3) 4804(3) 10912(3) 18(1)

C(37') 131(3) 3924(3) 11654(3) 20(1)

C(38') -403(3) 3950(3) 12584(3) 23(1)

C(39') -673(3) 4906(4) 12824(3) 24(1)

C(40') -382(3) 5808(3) 12120(3) 24(1)

C(41') 158(3) 5743(3) 11196(3) 20(1)

C(42') 1560(3) 5643(3) 9033(3) 18(1)

C(43') 2409(3) 5791(3) 9204(3) 21(1)

C(44') 3032(4) 6472(3) 8577(3) 25(1)

C(45') 2867(4) 7058(3) 7673(3) 26(1)

C(46') 2049(4) 6924(3) 7455(3) 23(1)

C(47') 1432(3) 6242(3) 8105(3) 21(1) ________________________________________________________________________________

78

Table 2.13. Anisotropic displacement parameters (Å2x 103) for 2.27. The anisotropic displacement factor exponent takes the form: -2π2[ h2 a*2U11 + ... + 2 h k a* b* U12 ]

______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

Ru(1) 19(1) 24(1) 14(1) -9(1) 1(1) -11(1)

Ru(1') 15(1) 23(1) 15(1) -6(1) -2(1) -10(1)

P(1) 19(1) 21(1) 13(1) -3(1) -2(1) -11(1)

P(1') 16(1) 21(1) 15(1) -6(1) 0(1) -11(1)

N(1) 20(2) 24(2) 17(2) -6(1) 0(1) -14(1)

N(2) 23(2) 23(1) 18(2) -6(1) -5(1) -12(1)

N(3) 19(2) 27(2) 22(2) -11(2) -4(1) -6(1)

N(1') 18(2) 22(1) 16(2) -6(1) -3(1) -10(1)

N(2') 20(2) 23(1) 15(2) -5(1) -4(1) -10(1)

N(3') 19(2) 27(2) 29(2) -11(2) -6(2) -11(1)

B(1) 24(2) 26(2) 18(3) -8(2) -5(2) -13(2)

B(1') 22(2) 19(2) 17(2) -5(2) -6(2) -9(2)

F(1) 29(1) 32(1) 22(1) -13(1) 1(1) -14(1)

F(2) 31(1) 54(1) 19(1) -11(1) 6(1) -22(1)

F(3) 39(2) 54(2) 31(2) 1(1) 0(1) -35(1)

F(4) 38(1) 38(1) 42(2) -10(1) -4(1) -28(1)

F(5) 29(1) 32(1) 24(1) -14(1) -2(1) -16(1)

F(6) 25(1) 28(1) 18(1) -9(1) -5(1) -9(1)

F(7) 29(1) 34(1) 20(1) -5(1) -10(1) -12(1)

F(8) 23(1) 27(1) 29(1) -7(1) -10(1) -1(1)

F(9) 24(1) 28(1) 24(1) -12(1) -2(1) -9(1)

F(10) 24(1) 26(1) 16(1) -8(1) -4(1) -10(1)

F(11) 23(1) 25(1) 37(2) -11(1) -14(1) -5(1)

F(12) 47(2) 24(1) 59(2) -14(1) -32(2) -1(1)

F(13) 55(2) 26(1) 43(2) -4(1) -21(1) -24(1)

F(14) 34(1) 38(1) 22(1) 0(1) -9(1) -27(1)

F(15) 20(1) 31(1) 24(1) -8(1) -6(1) -12(1)

F(16) 18(1) 31(1) 20(1) -6(1) -4(1) -12(1)

F(17) 25(1) 34(1) 18(1) -3(1) 0(1) -12(1)

79


______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

F(18) 35(1) 36(1) 18(1) -1(1) -10(1) -9(1)

F(19) 27(1) 40(1) 33(2) -2(1) -17(1) -14(1)

F(20) 21(1) 37(1) 27(1) -5(1) -7(1) -15(1)

F(1') 26(1) 33(1) 21(1) -11(1) -8(1) -10(1)

F(2') 32(1) 39(1) 36(2) -25(1) 0(1) -12(1)

F(3') 34(1) 33(1) 47(2) -20(1) -3(1) 2(1)

F(4') 22(1) 34(1) 31(1) 0(1) -7(1) -4(1)

F(5') 21(1) 29(1) 16(1) -5(1) -3(1) -9(1)

F(6') 22(1) 21(1) 25(1) -8(1) -4(1) -7(1)

F(7') 21(1) 34(1) 27(1) -9(1) -7(1) -2(1)

F(8') 19(1) 59(2) 29(1) -18(1) -1(1) -20(1)

F(9') 32(1) 43(1) 28(1) -12(1) 0(1) -28(1)

F(10') 25(1) 23(1) 27(1) -7(1) -5(1) -13(1)

F(11') 25(1) 22(1) 20(1) -5(1) -2(1) -13(1)

F(12') 33(1) 40(1) 17(1) 1(1) 0(1) -22(1)

F(13') 33(1) 59(2) 19(1) -20(1) 3(1) -18(1)

F(14') 36(1) 38(1) 30(1) -21(1) -6(1) -11(1)

F(15') 35(1) 23(1) 23(1) -7(1) -5(1) -15(1)

F(16') 30(1) 34(1) 18(1) -1(1) -8(1) -20(1)

F(17') 38(1) 51(1) 33(2) -12(1) -4(1) -32(1)

F(18') 51(2) 43(1) 22(1) -6(1) 6(1) -38(1)

F(19') 46(2) 37(1) 12(1) 2(1) -5(1) -22(1)

F(20') 32(1) 35(1) 14(1) -2(1) -8(1) -17(1)

C(1) 32(2) 37(2) 15(2) -14(2) 8(2) -18(2)

C(2) 32(2) 42(2) 25(2) -22(2) -1(2) -15(2)

C(3) 32(2) 45(2) 33(3) -27(2) 0(2) -20(2)

C(4) 37(2) 22(2) 29(3) -16(2) 0(2) -11(2)

C(5) 24(2) 30(2) 26(2) -18(2) 5(2) -10(2)

C(6) 23(2) 22(2) 14(2) -3(2) 0(2) -15(2)

C(7) 23(2) 30(2) 12(2) -4(2) 0(2) -18(2)

80


______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

C(8) 23(2) 36(2) 14(2) -8(2) 2(2) -20(2)

C(9) 22(2) 45(2) 36(3) -24(2) 2(2) -18(2)

C(10) 22(2) 37(2) 49(3) -21(2) -8(2) -7(2)

C(11) 22(2) 47(2) 41(3) -20(2) 1(2) -16(2)

C(12) 29(2) 70(3) 43(3) -34(3) 16(2) -35(2)

C(13) 30(2) 20(2) 21(2) 0(2) -9(2) -13(2)

C(14) 31(2) 29(2) 19(2) 0(2) -11(2) -16(2)

C(15) 39(2) 35(2) 24(2) -3(2) -13(2) -19(2)

C(16) 45(3) 26(2) 35(3) 1(2) -25(2) -16(2)

C(17) 48(3) 45(2) 12(2) 8(2) -11(2) -32(2)

C(18) 19(2) 26(2) 20(2) -7(2) 3(2) -12(2)

C(19) 26(2) 29(2) 20(2) -6(2) 3(2) -13(2)

C(20) 24(2) 35(2) 33(3) -6(2) -3(2) -17(2)

C(21) 25(2) 28(2) 26(2) -8(2) 1(2) -12(2)

C(22) 26(2) 22(2) 26(2) -9(2) -9(2) -10(2)

C(23) 43(2) 29(2) 27(2) 1(2) -18(2) -20(2)

C(24) 21(2) 22(2) 19(2) -7(2) -7(2) -6(2)

C(25) 20(2) 27(2) 19(2) -8(2) -4(2) -8(2)

C(26) 20(2) 33(2) 20(2) -9(2) -2(2) -9(2)

C(27) 27(2) 36(2) 18(2) 1(2) -3(2) -21(2)

C(28) 27(2) 27(2) 29(2) -3(2) -9(2) -16(2)

C(29) 17(2) 25(2) 14(2) -5(2) 0(2) -12(2)

C(30) 18(2) 24(2) 19(2) -5(2) -2(2) -13(2)

C(31) 20(2) 30(2) 15(2) -8(2) 0(2) -14(2)

C(32) 22(2) 26(2) 13(2) -3(2) -6(2) -10(2)

C(33) 19(2) 24(2) 18(2) -4(2) -6(2) -6(2)

C(34) 19(2) 25(2) 19(2) -9(2) 0(2) -11(2)

C(35) 22(2) 23(2) 11(2) -1(2) -4(2) -13(2)

C(36) 23(2) 23(2) 10(2) -5(2) -2(2) -10(2)

81


______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

C(37) 25(2) 26(2) 17(2) -6(2) -7(2) -10(2)

C(38) 34(2) 21(2) 26(2) -3(2) -14(2) -7(2)

C(39) 44(3) 23(2) 23(2) -1(2) -12(2) -18(2)

C(40) 29(2) 33(2) 11(2) -2(2) -4(2) -20(2)

C(41) 26(2) 29(2) 9(2) -3(2) 0(2) -19(2)

C(42) 20(2) 20(2) 18(2) -6(2) -4(2) -9(2)

C(43) 20(2) 25(2) 21(2) -6(2) -6(2) -9(2)

C(44) 26(2) 26(2) 27(2) -9(2) -13(2) -6(2)

C(45) 30(2) 24(2) 16(2) -5(2) -7(2) -8(2)

C(46) 23(2) 22(2) 16(2) -7(2) 2(2) -10(2)

C(47) 21(2) 22(2) 23(2) -9(2) -8(2) -6(2)

C(1') 29(2) 52(3) 19(2) 1(2) -12(2) -22(2)

C(2') 26(2) 26(2) 25(2) -1(2) -15(2) -5(2)

C(3') 18(2) 44(2) 27(2) -11(2) -8(2) -11(2)

C(4') 32(2) 37(2) 45(3) -12(2) -19(2) -16(2)

C(5') 23(2) 60(3) 37(3) -31(2) -13(2) -7(2)

C(6') 16(2) 25(2) 12(2) -6(2) 0(2) -10(2)

C(7') 23(2) 24(2) 15(2) -6(2) -3(2) -15(2)

C(8') 17(2) 22(2) 15(2) -5(2) 0(2) -14(2)

C(9') 20(2) 23(2) 24(2) -4(2) -4(2) -12(2)

C(10') 26(2) 28(2) 26(2) -8(2) 1(2) -13(2)

C(11') 30(2) 27(2) 20(2) -5(2) 1(2) -19(2)

C(12') 29(2) 28(2) 23(2) 1(2) -9(2) -14(2)

C(13') 19(2) 28(2) 24(2) -8(2) -5(2) -9(2)

C(14') 18(2) 34(2) 27(2) -18(2) 1(2) -12(2)

C(15') 39(3) 94(4) 74(4) -71(4) 18(3) -35(3)

C(16') 30(2) 40(2) 31(3) -19(2) 7(2) -9(2)

C(17') 36(3) 48(3) 22(3) -14(2) 4(2) -12(2)

C(18') 21(2) 23(2) 25(2) -4(2) -4(2) -10(2)

82


______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

C(19A) 34(5) 25(4) 35(6) -8(4) -9(4) -12(4)

C(20A) 28(4) 24(3) 19(4) 0(3) -8(3) -12(3)

C(21A) 30(5) 34(4) 29(5) 2(4) -5(4) -26(4)

C(19B) 28(5) 40(5) 34(6) 7(5) -16(4) -9(4)

C(20B) 35(5) 32(4) 22(5) -4(4) 1(4) -16(4)

C(21B) 24(4) 24(4) 29(5) 0(4) 4(4) -17(3)

C(22') 16(2) 33(2) 26(2) -13(2) -2(2) -11(2)

C(23') 25(2) 47(2) 22(2) -18(2) 1(2) -14(2)

C(24') 21(2) 19(2) 16(2) -2(2) -2(2) -12(2)

C(25') 13(2) 25(2) 23(2) -7(2) -1(2) -10(2)

C(26') 28(2) 27(2) 27(2) -13(2) 0(2) -16(2)

C(27') 19(2) 21(2) 33(3) -10(2) 2(2) -6(2)

C(28') 18(2) 22(2) 26(2) 0(2) -1(2) -11(2)

C(29') 17(2) 24(2) 16(2) -5(2) 0(2) -10(2)

C(30') 20(2) 25(2) 10(2) -4(2) 0(2) -12(2)

C(31') 18(2) 27(2) 14(2) -8(2) 0(2) -10(2)

C(32') 21(2) 35(2) 15(2) -11(2) -3(2) -5(2)

C(33') 19(2) 42(2) 15(2) -9(2) -1(2) -15(2)

C(34') 26(2) 36(2) 17(2) -11(2) 4(2) -20(2)

C(35') 21(2) 25(2) 15(2) -7(2) -1(2) -10(2)

C(36') 18(2) 22(2) 19(2) -6(2) -7(2) -9(2)

C(37') 15(2) 24(2) 23(2) -6(2) -6(2) -8(2)

C(38') 19(2) 30(2) 19(2) -3(2) -3(2) -12(2)

C(39') 18(2) 42(2) 15(2) -13(2) 0(2) -13(2)

C(40') 19(2) 32(2) 28(2) -16(2) -6(2) -7(2)

C(41') 20(2) 23(2) 20(2) -4(2) -6(2) -10(2)

C(42') 21(2) 18(2) 16(2) -5(2) -3(2) -9(2)

C(43') 24(2) 26(2) 14(2) -7(2) -3(2) -10(2)

C(44') 24(2) 34(2) 24(2) -15(2) 3(2) -18(2)

83


______________________________________________________________________________

U11 U22 U33 U23 U13 U12

______________________________________________________________________________

C(45') 34(2) 26(2) 19(2) -8(2) 6(2) -20(2)

C(46') 30(2) 27(2) 11(2) -4(2) 0(2) -15(2)

C(47') 24(2) 25(2) 14(2) -5(2) -3(2) -11(2) ______________________________________________________________________________

Table 2.14. Bond lengths and angles for 2.27

______________________________________________________________________________

Ru(1)-N(3) 2.056(4)

Ru(1)-C(4) 2.160(4)

Ru(1)-C(3) 2.175(4)

Ru(1)-N(1) 2.175(3)

Ru(1)-C(5) 2.175(4)

Ru(1)-C(2) 2.185(4)

Ru(1)-C(1) 2.191(4)

Ru(1)-P(1) 2.4183(9)

Ru(1')-N(3') 2.055(4)

Ru(1')-C(3') 2.138(4)

Ru(1')-C(4') 2.164(4)

Ru(1')-C(2') 2.173(4)

Ru(1')-C(5') 2.180(4)

Ru(1')-C(1') 2.189(4)

Ru(1')-N(1') 2.194(3)

Ru(1')-P(1') 2.3957(9)

P(1)-C(6) 1.828(4)

P(1)-C(18) 1.880(4)

P(1)-C(14) 1.894(4)

P(1')-C(6') 1.814(4)

P(1')-C(18') 1.878(4)

P(1')-C(14') 1.892(4)

N(1)-C(6) 1.321(5)

N(1)-C(8) 1.385(5)

N(2)-C(6) 1.351(5)

N(2)-C(7) 1.379(5)

N(2)-C(13) 1.457(5)

N(3)-C(22) 1.141(6)

N(1')-C(6') 1.342(5)

N(1')-C(8') 1.373(5)

N(2')-C(6') 1.356(5)

N(2')-C(7') 1.371(5)

N(2')-C(13') 1.453(5)

N(3')-C(22') 1.140(6)

B(1)-C(30) 1.644(6)

B(1)-C(36) 1.644(6)

B(1)-C(24) 1.645(7)

B(1)-C(42) 1.656(6)

B(1')-C(42') 1.649(6)

B(1')-C(36') 1.651(6)

B(1')-C(30') 1.653(6)

B(1')-C(24') 1.663(6)

F(1)-C(25) 1.350(5)

F(2)-C(26) 1.340(5)

F(3)-C(27) 1.346(5)

F(4)-C(28) 1.336(5)

84


______________________________________________________________________________

F(5)-C(29) 1.352(5)

F(6)-C(31) 1.337(5)

F(7)-C(32) 1.347(5)

F(8)-C(33) 1.335(5)

F(9)-C(34) 1.337(5)

F(10)-C(35) 1.355(4)

F(11)-C(37) 1.344(5)

F(12)-C(38) 1.343(5)

F(13)-C(39) 1.340(5)

F(14)-C(40) 1.342(5)

F(15)-C(41) 1.355(5)

F(16)-C(47) 1.353(5)

F(17)-C(46) 1.345(5)

F(18)-C(45) 1.342(5)

F(19)-C(44) 1.350(5)

F(20)-C(43) 1.348(5)

F(1')-C(25') 1.359(5)

F(2')-C(26') 1.340(5)

F(3')-C(27') 1.331(5)

F(4')-C(28') 1.349(5)

F(5')-C(29') 1.340(5)

F(6')-C(31') 1.353(5)

F(7')-C(32') 1.349(5)

F(8')-C(33') 1.355(5)

F(9')-C(34') 1.340(5)

F(10')-C(35') 1.352(5)

F(11')-C(37') 1.354(5)

F(12')-C(38') 1.351(5)

F(13')-C(39') 1.341(5)

F(14')-C(40') 1.341(5)

F(15')-C(41') 1.355(5)

F(16')-C(43') 1.352(5)

F(17')-C(44') 1.349(5)

F(18')-C(45') 1.334(5)

F(19')-C(46') 1.355(5)

F(20')-C(47') 1.351(5)

C(1)-C(2) 1.420(7)

C(1)-C(5) 1.433(7)

C(1)-H(1) 0.9500

C(2)-C(3) 1.402(7)

C(2)-H(2) 0.9500

C(3)-C(4) 1.422(7)

C(3)-H(3) 0.9500

C(4)-C(5) 1.435(7)

C(4)-H(4) 0.9500

C(5)-H(5) 0.9500

C(7)-C(8) 1.348(6)

C(7)-H(1N) 0.9500

C(8)-C(9) 1.527(6)

C(9)-C(12) 1.523(7)

C(9)-C(11) 1.525(6)

C(9)-C(10) 1.541(7)

C(10)-H(10A) 0.9800

C(10)-H(10B) 0.9800

C(10)-H(10C) 0.9800

C(11)-H(11A) 0.9800

C(11)-H(11B) 0.9800

C(11)-H(11C) 0.9800

C(12)-H(12A) 0.9800

C(12)-H(12B) 0.9800

C(12)-H(12C) 0.9800

C(13)-H(13A) 0.9800

C(13)-H(13B) 0.9800

C(13)-H(13C) 0.9800

85


______________________________________________________________________________

C(14)-C(17) 1.541(6)

C(14)-C(16) 1.541(6)

C(14)-C(15) 1.541(6)

C(15)-H(15A) 0.9800

C(15)-H(15B) 0.9800

C(15)-H(15C) 0.9800

C(16)-H(16A) 0.9800

C(16)-H(16B) 0.9800

C(16)-H(16C) 0.9800

C(17)-H(17A) 0.9800

C(17)-H(17B) 0.9800

C(17)-H(17C) 0.9800

C(18)-C(20) 1.530(6)

C(18)-C(19) 1.531(6)

C(18)-C(21) 1.533(6)

C(19)-H(19A) 0.9800

C(19)-H(19B) 0.9800

C(19)-H(19C) 0.9800

C(20)-H(20A) 0.9800

C(20)-H(20B) 0.9800

C(20)-H(20C) 0.9800

C(21)-H(21A) 0.9800

C(21)-H(21B) 0.9800

C(21)-H(21C) 0.9800

C(22)-C(23) 1.460(6)

C(23)-H(23A) 0.9800

C(23)-H(23B) 0.9800

C(23)-H(23C) 0.9800

C(24)-C(25) 1.373(6)

C(24)-C(29) 1.394(6)

C(25)-C(26) 1.394(6)

C(26)-C(27) 1.360(6)

C(27)-C(28) 1.387(7)

C(28)-C(29) 1.376(6)

C(30)-C(35) 1.384(6)

C(30)-C(31) 1.410(6)

C(31)-C(32) 1.369(6)

C(32)-C(33) 1.372(6)

C(33)-C(34) 1.392(6)

C(34)-C(35) 1.381(6)

C(36)-C(41) 1.382(6)

C(36)-C(37) 1.396(6)

C(37)-C(38) 1.370(6)

C(38)-C(39) 1.383(7)

C(39)-C(40) 1.358(6)

C(40)-C(41) 1.383(6)

C(42)-C(47) 1.387(6)

C(42)-C(43) 1.398(6)

C(43)-C(44) 1.391(6)

C(44)-C(45) 1.361(6)

C(45)-C(46) 1.369(6)

C(46)-C(47) 1.379(6)

C(1')-C(5') 1.411(7)

C(1')-C(2') 1.425(7)

C(1')-H(1') 0.9500

C(2')-C(3') 1.408(6)

C(2')-H(2') 0.9500

C(3')-C(4') 1.414(6)

C(3')-H(3') 0.9500

C(4')-C(5') 1.423(7)

C(4')-H(4') 0.9500

C(5')-H(5') 0.9500

C(7')-C(8') 1.367(6)

C(7')-H(7') 0.9500

86


______________________________________________________________________________

C(8')-C(9') 1.516(5)

C(9')-C(11') 1.527(6)

C(9')-C(12') 1.527(6)

C(9')-C(10') 1.539(5)

C(10')-H(10D) 0.9800

C(10')-H(10E) 0.9800

C(10')-H(10F) 0.9800

C(11')-H(11D) 0.9800

C(11')-H(11E) 0.9800

C(11')-H(11F) 0.9800

C(12')-H(12D) 0.9800

C(12')-H(12E) 0.9800

C(12')-H(12F) 0.9800

C(13')-H(13D) 0.9800

C(13')-H(13E) 0.9800

C(13')-H(13F) 0.9800

C(14')-C(17') 1.517(7)

C(14')-C(16') 1.530(6)

C(14')-C(15') 1.535(6)

C(15')-H(15D) 0.9800

C(15')-H(15E) 0.9800

C(15')-H(15F) 0.9800

C(16')-H(16D) 0.9800

C(16')-H(16E) 0.9800

C(16')-H(16F) 0.9800

C(17')-H(17D) 0.9800

C(17')-H(17E) 0.9800

C(17')-H(17F) 0.9800

C(18')-C(20B) 1.481(10)

C(18')-C(19B) 1.490(10)

C(18')-C(21A) 1.513(9)

C(18')-C(19A) 1.542(9)

C(18')-C(21B) 1.579(9)

C(18')-C(20A) 1.612(9)

C(19A)-H(19D) 0.9800

C(19A)-H(19E) 0.9800

C(19A)-H(19F) 0.9800

C(20A)-H(20D) 0.9800

C(20A)-H(20E) 0.9800

C(20A)-H(20F) 0.9800

C(21A)-H(21D) 0.9800

C(21A)-H(21E) 0.9800

C(21A)-H(21F) 0.9800

C(19B)-H(19G) 0.9800

C(19B)-H(19H) 0.9800

C(19B)-H(19I) 0.9800

C(20B)-H(20G) 0.9800

C(20B)-H(20H) 0.9800

C(20B)-H(20I) 0.9800

C(21B)-H(21G) 0.9800

C(21B)-H(21H) 0.9800

C(21B)-H(21I) 0.9800

C(22')-C(23') 1.451(6)

C(23')-H(23D) 0.9800

C(23')-H(23E) 0.9800

C(23')-H(23F) 0.9800

C(24')-C(25') 1.367(6)

C(24')-C(29') 1.395(6)

C(25')-C(26') 1.394(6)

C(26')-C(27') 1.377(7)

C(27')-C(28') 1.359(7)

C(28')-C(29') 1.392(6)

C(30')-C(35') 1.384(6)

C(30')-C(31') 1.387(6)

87


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C(31')-C(32') 1.374(6)

C(32')-C(33') 1.361(7)

C(33')-C(34') 1.376(6)

C(34')-C(35') 1.389(6)

C(36')-C(41') 1.384(5)

C(36')-C(37') 1.391(6)

C(37')-C(38') 1.376(6)

C(38')-C(39') 1.373(6)

C(39')-C(40') 1.377(6)

C(40')-C(41') 1.382(6)

C(42')-C(43') 1.390(6)

C(42')-C(47') 1.405(6)

C(43')-C(44') 1.361(6)

C(44')-C(45') 1.384(7)

C(45')-C(46') 1.386(6)

C(46')-C(47') 1.365(6)

N(3)-Ru(1)-C(4) 89.61(16)

N(3)-Ru(1)-C(3) 113.82(17)

C(4)-Ru(1)-C(3) 38.28(18)

N(3)-Ru(1)-N(1) 84.47(14)

C(4)-Ru(1)-N(1) 148.20(15)

C(3)-Ru(1)-N(1) 161.70(16)

N(3)-Ru(1)-C(5) 102.75(15)

C(4)-Ru(1)-C(5) 38.66(17)

C(3)-Ru(1)-C(5) 64.24(17)

N(1)-Ru(1)-C(5) 112.69(15)

N(3)-Ru(1)-C(2) 150.81(16)

C(4)-Ru(1)-C(2) 63.43(18)

C(3)-Ru(1)-C(2) 37.50(18)

N(1)-Ru(1)-C(2) 124.24(15)

C(5)-Ru(1)-C(2) 63.73(18)

N(3)-Ru(1)-C(1) 140.29(15)

C(4)-Ru(1)-C(1) 64.04(17)

C(3)-Ru(1)-C(1) 63.55(17)

N(1)-Ru(1)-C(1) 102.29(15)

C(5)-Ru(1)-C(1) 38.32(17)

C(2)-Ru(1)-C(1) 37.86(17)

N(3)-Ru(1)-P(1) 94.73(9)

C(4)-Ru(1)-P(1) 145.09(13)

C(3)-Ru(1)-P(1) 110.39(12)

N(1)-Ru(1)-P(1) 66.68(8)

C(5)-Ru(1)-P(1) 162.40(13)

C(2)-Ru(1)-P(1) 101.38(12)

C(1)-Ru(1)-P(1) 124.10(12)

N(3')-Ru(1')-C(3') 90.30(16)

N(3')-Ru(1')-C(4') 115.31(17)

C(3')-Ru(1')-C(4') 38.38(17)

N(3')-Ru(1')-C(2') 101.42(15)

C(3')-Ru(1')-C(2') 38.14(17)

C(4')-Ru(1')-C(2') 64.38(17)

N(3')-Ru(1')-C(5') 152.57(16)

C(3')-Ru(1')-C(5') 63.60(17)

C(4')-Ru(1')-C(5') 38.2(2)

C(2')-Ru(1')-C(5') 63.82(17)

N(3')-Ru(1')-C(1') 138.38(16)

C(3')-Ru(1')-C(1') 63.39(18)

C(4')-Ru(1')-C(1') 63.74(18)

C(2')-Ru(1')-C(1') 38.15(18)

C(5')-Ru(1')-C(1') 37.68(19)

N(3')-Ru(1')-N(1') 83.67(13)

C(3')-Ru(1')-N(1') 151.41(15)

C(4')-Ru(1')-N(1') 160.91(16)

C(2')-Ru(1')-N(1') 115.94(14)

88


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C(5')-Ru(1')-N(1') 123.21(16)

C(1')-Ru(1')-N(1') 103.98(15)

N(3')-Ru(1')-P(1') 92.95(9)

C(3')-Ru(1')-P(1') 141.47(13)

C(4')-Ru(1')-P(1') 107.94(12)

C(2')-Ru(1')-P(1') 165.54(12)

C(5')-Ru(1')-P(1') 102.35(12)

C(1')-Ru(1')-P(1') 127.99(13)

N(1')-Ru(1')-P(1') 66.95(8)

C(6)-P(1)-C(18) 110.27(19)

C(6)-P(1)-C(14) 106.18(18)

C(18)-P(1)-C(14) 110.3(2)

C(6)-P(1)-Ru(1) 82.09(12)

C(18)-P(1)-Ru(1) 127.16(13)

C(14)-P(1)-Ru(1) 114.92(14)

C(6')-P(1')-C(18') 111.55(18)

C(6')-P(1')-C(14') 105.18(17)

C(18')-P(1')-C(14') 111.53(19)

C(6')-P(1')-Ru(1') 82.75(12)

C(18')-P(1')-Ru(1') 124.11(13)

C(14')-P(1')-Ru(1') 115.99(14)

C(6)-N(1)-C(8) 108.1(3)

C(6)-N(1)-Ru(1) 105.1(3)

C(8)-N(1)-Ru(1) 146.9(3)

C(6)-N(2)-C(7) 106.5(3)

C(6)-N(2)-C(13) 130.3(3)

C(7)-N(2)-C(13) 123.2(3)

C(22)-N(3)-Ru(1) 172.5(3)

C(6')-N(1')-C(8') 107.9(3)

C(6')-N(1')-Ru(1') 102.9(2)

C(8')-N(1')-Ru(1') 148.6(2)

C(6')-N(2')-C(7') 106.5(3)

C(6')-N(2')-C(13') 129.1(3)

C(7')-N(2')-C(13') 124.3(3)

C(22')-N(3')-Ru(1') 174.4(3)

C(30)-B(1)-C(36) 111.1(3)

C(30)-B(1)-C(24) 100.9(3)

C(36)-B(1)-C(24) 115.8(3)

C(30)-B(1)-C(42) 114.7(3)

C(36)-B(1)-C(42) 100.1(3)

C(24)-B(1)-C(42) 114.9(3)

C(42')-B(1')-C(36') 114.3(3)

C(42')-B(1')-C(30') 114.4(3)

C(36')-B(1')-C(30') 101.1(3)

C(42')-B(1')-C(24') 100.6(3)

C(36')-B(1')-C(24') 114.4(3)

C(30')-B(1')-C(24') 112.7(3)

C(2)-C(1)-C(5) 107.6(4)

C(2)-C(1)-Ru(1) 70.8(2)

C(5)-C(1)-Ru(1) 70.2(2)

C(2)-C(1)-H(1) 126.2

C(5)-C(1)-H(1) 126.2

Ru(1)-C(1)-H(1) 124.3

C(3)-C(2)-C(1) 109.1(4)

C(3)-C(2)-Ru(1) 70.8(2)

C(1)-C(2)-Ru(1) 71.3(2)

C(3)-C(2)-H(2) 125.4

C(1)-C(2)-H(2) 125.4

Ru(1)-C(2)-H(2) 124.0

C(2)-C(3)-C(4) 108.0(4)

C(2)-C(3)-Ru(1) 71.7(2)

C(4)-C(3)-Ru(1) 70.3(2)

C(2)-C(3)-H(3) 126.0

C(4)-C(3)-H(3) 126.0

89


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Ru(1)-C(3)-H(3) 123.7

C(3)-C(4)-C(5) 108.1(4)

C(3)-C(4)-Ru(1) 71.4(2)

C(5)-C(4)-Ru(1) 71.2(2)

C(3)-C(4)-H(4) 125.9

C(5)-C(4)-H(4) 125.9

Ru(1)-C(4)-H(4) 123.1

C(1)-C(5)-C(4) 107.1(4)

C(1)-C(5)-Ru(1) 71.4(2)

C(4)-C(5)-Ru(1) 70.1(2)

C(1)-C(5)-H(5) 126.4

C(4)-C(5)-H(5) 126.4

Ru(1)-C(5)-H(5) 123.7

N(1)-C(6)-N(2) 110.0(3)

N(1)-C(6)-P(1) 106.0(3)

N(2)-C(6)-P(1) 143.7(3)

C(8)-C(7)-N(2) 108.5(4)

C(8)-C(7)-H(1N) 125.7

N(2)-C(7)-H(1N) 125.7

C(7)-C(8)-N(1) 106.9(3)

C(7)-C(8)-C(9) 128.0(4)

N(1)-C(8)-C(9) 124.9(4)

C(12)-C(9)-C(11) 109.7(4)

C(12)-C(9)-C(8) 108.5(4)

C(11)-C(9)-C(8) 109.1(3)

C(12)-C(9)-C(10) 109.0(4)

C(11)-C(9)-C(10) 110.0(4)

C(8)-C(9)-C(10) 110.5(4)

C(9)-C(10)-H(10A) 109.5

C(9)-C(10)-H(10B) 109.5

H(10A)-C(10)-H(10B) 109.5

C(9)-C(10)-H(10C) 109.5

H(10A)-C(10)-H(10C) 109.5

H(10B)-C(10)-H(10C) 109.5

C(9)-C(11)-H(11A) 109.5

C(9)-C(11)-H(11B) 109.5

H(11A)-C(11)-H(11B) 109.5

C(9)-C(11)-H(11C) 109.5

H(11A)-C(11)-H(11C) 109.5

H(11B)-C(11)-H(11C) 109.5

C(9)-C(12)-H(12A) 109.5

C(9)-C(12)-H(12B) 109.5

H(12A)-C(12)-H(12B) 109.5

C(9)-C(12)-H(12C) 109.5

H(12A)-C(12)-H(12C) 109.5

H(12B)-C(12)-H(12C) 109.5

N(2)-C(13)-H(13A) 109.5

N(2)-C(13)-H(13B) 109.5

H(13A)-C(13)-H(13B) 109.5

N(2)-C(13)-H(13C) 109.5

H(13A)-C(13)-H(13C) 109.5

H(13B)-C(13)-H(13C) 109.5

C(17)-C(14)-C(16) 108.6(4)

C(17)-C(14)-C(15) 110.6(4)

C(16)-C(14)-C(15) 107.9(3)

C(17)-C(14)-P(1) 106.2(3)

C(16)-C(14)-P(1) 115.3(3)

C(15)-C(14)-P(1) 108.3(3)

C(14)-C(15)-H(15A) 109.5

C(14)-C(15)-H(15B) 109.5

H(15A)-C(15)-H(15B) 109.5

C(14)-C(15)-H(15C) 109.5

H(15A)-C(15)-H(15C) 109.5

H(15B)-C(15)-H(15C) 109.5

90


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C(14)-C(16)-H(16A) 109.5

C(14)-C(16)-H(16B) 109.5

H(16A)-C(16)-H(16B) 109.5

C(14)-C(16)-H(16C) 109.5

H(16A)-C(16)-H(16C) 109.5

H(16B)-C(16)-H(16C) 109.5

C(14)-C(17)-H(17A) 109.5

C(14)-C(17)-H(17B) 109.5

H(17A)-C(17)-H(17B) 109.5

C(14)-C(17)-H(17C) 109.5

H(17A)-C(17)-H(17C) 109.5

H(17B)-C(17)-H(17C) 109.5

C(20)-C(18)-C(19) 107.8(4)

C(20)-C(18)-C(21) 110.8(3)

C(19)-C(18)-C(21) 106.9(4)

C(20)-C(18)-P(1) 108.3(3)

C(19)-C(18)-P(1) 107.3(3)

C(21)-C(18)-P(1) 115.5(3)

C(18)-C(19)-H(19A) 109.5

C(18)-C(19)-H(19B) 109.5

H(19A)-C(19)-H(19B) 109.5

C(18)-C(19)-H(19C) 109.5

H(19A)-C(19)-H(19C) 109.5

H(19B)-C(19)-H(19C) 109.5

C(18)-C(20)-H(20A) 109.5

C(18)-C(20)-H(20B) 109.5

H(20A)-C(20)-H(20B) 109.5

C(18)-C(20)-H(20C) 109.5

H(20A)-C(20)-H(20C) 109.5

H(20B)-C(20)-H(20C) 109.5

C(18)-C(21)-H(21A) 109.5

C(18)-C(21)-H(21B) 109.5

H(21A)-C(21)-H(21B) 109.5

C(18)-C(21)-H(21C) 109.5

H(21A)-C(21)-H(21C) 109.5

H(21B)-C(21)-H(21C) 109.5

N(3)-C(22)-C(23) 177.3(4)

C(22)-C(23)-H(23A) 109.5

C(22)-C(23)-H(23B) 109.5

H(23A)-C(23)-H(23B) 109.5

C(22)-C(23)-H(23C) 109.5

H(23A)-C(23)-H(23C) 109.5

H(23B)-C(23)-H(23C) 109.5

C(25)-C(24)-C(29) 113.6(4)

C(25)-C(24)-B(1) 126.7(4)

C(29)-C(24)-B(1) 118.7(3)

F(1)-C(25)-C(24) 121.1(4)

F(1)-C(25)-C(26) 115.0(4)

C(24)-C(25)-C(26) 123.9(4)

F(2)-C(26)-C(27) 120.7(4)

F(2)-C(26)-C(25) 119.7(4)

C(27)-C(26)-C(25) 119.6(4)

F(3)-C(27)-C(26) 120.6(4)

F(3)-C(27)-C(28) 119.6(4)

C(26)-C(27)-C(28) 119.7(4)

F(4)-C(28)-C(29) 121.5(4)

F(4)-C(28)-C(27) 120.3(4)

C(29)-C(28)-C(27) 118.2(4)

F(5)-C(29)-C(28) 115.4(3)

F(5)-C(29)-C(24) 119.6(3)

C(28)-C(29)-C(24) 125.0(4)

C(35)-C(30)-C(31) 113.0(3)

C(35)-C(30)-B(1) 128.2(4)

C(31)-C(30)-B(1) 118.5(3)

91


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F(6)-C(31)-C(32) 116.7(4)

F(6)-C(31)-C(30) 119.2(3)

C(32)-C(31)-C(30) 124.1(4)

F(7)-C(32)-C(31) 120.0(4)

F(7)-C(32)-C(33) 119.6(3)

C(31)-C(32)-C(33) 120.5(4)

F(8)-C(33)-C(32) 121.3(4)

F(8)-C(33)-C(34) 120.4(4)

C(32)-C(33)-C(34) 118.3(4)

F(9)-C(34)-C(35) 120.8(4)

F(9)-C(34)-C(33) 119.7(3)

C(35)-C(34)-C(33) 119.4(4)

F(10)-C(35)-C(34) 114.8(3)

F(10)-C(35)-C(30) 120.4(3)

C(34)-C(35)-C(30) 124.8(4)

C(41)-C(36)-C(37) 113.5(4)

C(41)-C(36)-B(1) 126.9(3)

C(37)-C(36)-B(1) 119.0(4)

F(11)-C(37)-C(38) 116.8(4)

F(11)-C(37)-C(36) 119.5(4)

C(38)-C(37)-C(36) 123.7(4)

F(12)-C(38)-C(37) 121.0(4)

F(12)-C(38)-C(39) 119.3(4)

C(37)-C(38)-C(39) 119.7(4)

F(13)-C(39)-C(40) 120.6(4)

F(13)-C(39)-C(38) 120.2(4)

C(40)-C(39)-C(38) 119.2(4)

F(14)-C(40)-C(39) 120.1(4)

F(14)-C(40)-C(41) 120.6(4)

C(39)-C(40)-C(41) 119.3(4)

F(15)-C(41)-C(36) 121.4(3)

F(15)-C(41)-C(40) 114.2(4)

C(36)-C(41)-C(40) 124.5(4)

C(47)-C(42)-C(43) 112.8(4)

C(47)-C(42)-B(1) 119.4(4)

C(43)-C(42)-B(1) 126.7(4)

F(20)-C(43)-C(44) 115.8(3)

F(20)-C(43)-C(42) 121.1(4)

C(44)-C(43)-C(42) 123.1(4)

F(19)-C(44)-C(45) 119.9(4)

F(19)-C(44)-C(43) 119.5(4)

C(45)-C(44)-C(43) 120.5(4)

F(18)-C(45)-C(44) 120.7(4)

F(18)-C(45)-C(46) 120.2(4)

C(44)-C(45)-C(46) 119.1(4)

F(17)-C(46)-C(45) 120.5(4)

F(17)-C(46)-C(47) 120.5(4)

C(45)-C(46)-C(47) 119.0(4)

F(16)-C(47)-C(46) 115.9(4)

F(16)-C(47)-C(42) 118.7(4)

C(46)-C(47)-C(42) 125.4(4)

C(5')-C(1')-C(2') 108.4(4)

C(5')-C(1')-Ru(1') 70.8(3)

C(2')-C(1')-Ru(1') 70.3(2)

C(5')-C(1')-H(1') 125.8

C(2')-C(1')-H(1') 125.8

Ru(1')-C(1')-H(1') 124.7

C(3')-C(2')-C(1') 106.7(4)

C(3')-C(2')-Ru(1') 69.6(2)

C(1')-C(2')-Ru(1') 71.5(2)

C(3')-C(2')-H(2') 126.7

C(1')-C(2')-H(2') 126.7

Ru(1')-C(2')-H(2') 123.9

C(2')-C(3')-C(4') 109.9(4)

92


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C(2')-C(3')-Ru(1') 72.3(2)

C(4')-C(3')-Ru(1') 71.8(2)

C(2')-C(3')-H(3') 125.1

C(4')-C(3')-H(3') 125.1

Ru(1')-C(3')-H(3') 122.4

C(3')-C(4')-C(5') 106.6(4)

C(3')-C(4')-Ru(1') 69.8(2)

C(5')-C(4')-Ru(1') 71.5(2)

C(3')-C(4')-H(4') 126.7

C(5')-C(4')-H(4') 126.7

Ru(1')-C(4')-H(4') 123.7

C(1')-C(5')-C(4') 108.4(4)

C(1')-C(5')-Ru(1') 71.5(2)

C(4')-C(5')-Ru(1') 70.3(3)

C(1')-C(5')-H(5') 125.8

C(4')-C(5')-H(5') 125.8

Ru(1')-C(5')-H(5') 124.1

N(1')-C(6')-N(2') 109.8(3)

N(1')-C(6')-P(1') 106.1(3)

N(2')-C(6')-P(1') 143.7(3)

C(8')-C(7')-N(2') 108.7(3)

C(8')-C(7')-H(7') 125.6

N(2')-C(7')-H(7') 125.6

C(7')-C(8')-N(1') 107.0(3)

C(7')-C(8')-C(9') 128.1(4)

N(1')-C(8')-C(9') 124.6(3)

C(8')-C(9')-C(11') 109.9(3)

C(8')-C(9')-C(12') 107.8(3)

C(11')-C(9')-C(12') 108.9(3)

C(8')-C(9')-C(10') 111.3(3)

C(11')-C(9')-C(10') 109.9(3)

C(12')-C(9')-C(10') 109.0(3)

C(9')-C(10')-H(10D) 109.5

C(9')-C(10')-H(10E) 109.5

H(10D)-C(10')-H(10E) 109.5

C(9')-C(10')-H(10F) 109.5

H(10D)-C(10')-H(10F) 109.5

H(10E)-C(10')-H(10F) 109.5

C(9')-C(11')-H(11D) 109.5

C(9')-C(11')-H(11E) 109.5

H(11D)-C(11')-H(11E) 109.5

C(9')-C(11')-H(11F) 109.5

H(11D)-C(11')-H(11F) 109.5

H(11E)-C(11')-H(11F) 109.5

C(9')-C(12')-H(12D) 109.5

C(9')-C(12')-H(12E) 109.5

H(12D)-C(12')-H(12E) 109.5

C(9')-C(12')-H(12F) 109.5

H(12D)-C(12')-H(12F) 109.5

H(12E)-C(12')-H(12F) 109.5

N(2')-C(13')-H(13D) 109.5

N(2')-C(13')-H(13E) 109.5

H(13D)-C(13')-H(13E) 109.5

N(2')-C(13')-H(13F) 109.5

H(13D)-C(13')-H(13F) 109.5

H(13E)-C(13')-H(13F) 109.5

C(17')-C(14')-C(16') 107.7(4)

C(17')-C(14')-C(15') 110.7(5)

C(16')-C(14')-C(15') 108.6(4)

C(17')-C(14')-P(1') 107.1(3)

C(16')-C(14')-P(1') 115.4(3)

C(15')-C(14')-P(1') 107.5(3)

C(14')-C(15')-H(15D) 109.5

C(14')-C(15')-H(15E) 109.5

93


______________________________________________________________________________

H(15D)-C(15')-H(15E) 109.5

C(14')-C(15')-H(15F) 109.5

H(15D)-C(15')-H(15F) 109.5

H(15E)-C(15')-H(15F) 109.5

C(14')-C(16')-H(16D) 109.5

C(14')-C(16')-H(16E) 109.5

H(16D)-C(16')-H(16E) 109.5

C(14')-C(16')-H(16F) 109.5

H(16D)-C(16')-H(16F) 109.5

H(16E)-C(16')-H(16F) 109.5

C(14')-C(17')-H(17D) 109.5

C(14')-C(17')-H(17E) 109.5

H(17D)-C(17')-H(17E) 109.5

C(14')-C(17')-H(17F) 109.5

H(17D)-C(17')-H(17F) 109.5

H(17E)-C(17')-H(17F) 109.5

C(20B)-C(18')-C(19B) 111.3(7)

C(20B)-C(18')-C(21A) 61.0(6)

C(19B)-C(18')-C(21A) 136.1(6)

C(20B)-C(18')-C(19A) 128.5(6)

C(19B)-C(18')-C(19A) 36.4(6)

C(21A)-C(18')-C(19A) 110.8(6)

C(20B)-C(18')-C(21B) 107.6(5)

C(19B)-C(18')-C(21B) 109.3(6)

C(21A)-C(18')-C(21B) 48.0(5)

C(19A)-C(18')-C(21B) 73.2(5)

C(20B)-C(18')-C(20A) 46.5(5)

C(19B)-C(18')-C(20A) 71.1(6)

C(21A)-C(18')-C(20A) 106.0(6)

C(19A)-C(18')-C(20A) 103.2(6)

C(21B)-C(18')-C(20A) 144.7(5)

C(20B)-C(18')-P(1') 108.4(4)

C(19B)-C(18')-P(1') 115.9(5)

C(21A)-C(18')-P(1') 106.8(4)

C(19A)-C(18')-P(1') 121.6(5)

C(21B)-C(18')-P(1') 103.7(4)

C(20A)-C(18')-P(1') 107.4(4)

C(18')-C(19A)-H(19D) 109.5

C(18')-C(19A)-H(19E) 109.5

C(18')-C(19A)-H(19F) 109.5

C(18')-C(20A)-H(20D) 109.5

C(18')-C(20A)-H(20E) 109.5

C(18')-C(20A)-H(20F) 109.5

C(18')-C(21A)-H(21D) 109.5

C(18')-C(21A)-H(21E) 109.5

C(18')-C(21A)-H(21F) 109.5

C(18')-C(19B)-H(19G) 109.5

C(18')-C(19B)-H(19H) 109.5

H(19G)-C(19B)-H(19H) 109.5

C(18')-C(19B)-H(19I) 109.5

H(19G)-C(19B)-H(19I) 109.5

H(19H)-C(19B)-H(19I) 109.5

C(18')-C(20B)-H(20G) 109.5

C(18')-C(20B)-H(20H) 109.5

H(20G)-C(20B)-H(20H) 109.5

C(18')-C(20B)-H(20I) 109.5

H(20G)-C(20B)-H(20I) 109.5

H(20H)-C(20B)-H(20I) 109.5

C(18')-C(21B)-H(21G) 109.5

C(18')-C(21B)-H(21H) 109.5

H(21G)-C(21B)-H(21H) 109.5

C(18')-C(21B)-H(21I) 109.5

H(21G)-C(21B)-H(21I) 109.5

H(21H)-C(21B)-H(21I) 109.5

94


______________________________________________________________________________

N(3')-C(22')-C(23') 176.0(4)

C(22')-C(23')-H(23D) 109.5

C(22')-C(23')-H(23E) 109.5

H(23D)-C(23')-H(23E) 109.5

C(22')-C(23')-H(23F) 109.5

H(23D)-C(23')-H(23F) 109.5

H(23E)-C(23')-H(23F) 109.5

C(25')-C(24')-C(29') 113.8(3)

C(25')-C(24')-B(1') 120.8(4)

C(29')-C(24')-B(1') 125.1(4)

F(1')-C(25')-C(24') 120.5(3)

F(1')-C(25')-C(26') 114.4(4)

C(24')-C(25')-C(26') 125.1(4)

F(2')-C(26')-C(27') 120.7(3)

F(2')-C(26')-C(25') 120.6(4)

C(27')-C(26')-C(25') 118.6(4)

F(3')-C(27')-C(28') 121.6(4)

F(3')-C(27')-C(26') 119.7(4)

C(28')-C(27')-C(26') 118.7(4)

F(4')-C(28')-C(27') 120.3(3)

F(4')-C(28')-C(29') 118.8(4)

C(27')-C(28')-C(29') 120.9(4)

F(5')-C(29')-C(28') 116.0(4)

F(5')-C(29')-C(24') 121.4(3)

C(28')-C(29')-C(24') 122.6(4)

C(35')-C(30')-C(31') 113.1(4)

C(35')-C(30')-B(1') 126.0(3)

C(31')-C(30')-B(1') 120.1(4)

F(6')-C(31')-C(32') 116.6(3)

F(6')-C(31')-C(30') 118.9(3)

C(32')-C(31')-C(30') 124.5(4)

F(7')-C(32')-C(33') 119.8(4)

F(7')-C(32')-C(31') 120.5(4)

C(33')-C(32')-C(31') 119.7(4)

F(8')-C(33')-C(32') 121.2(4)

F(8')-C(33')-C(34') 119.4(4)

C(32')-C(33')-C(34') 119.3(4)

F(9')-C(34')-C(33') 120.1(4)

F(9')-C(34')-C(35') 121.0(4)

C(33')-C(34')-C(35') 118.9(4)

F(10')-C(35')-C(30') 121.8(3)

F(10')-C(35')-C(34') 113.8(4)

C(30')-C(35')-C(34') 124.4(4)

C(41')-C(36')-C(37') 113.0(4)

C(41')-C(36')-B(1') 127.5(4)

C(37')-C(36')-B(1') 119.0(3)

F(11')-C(37')-C(38') 115.8(4)

F(11')-C(37')-C(36') 119.4(4)

C(38')-C(37')-C(36') 124.8(4)

F(12')-C(38')-C(39') 120.0(4)

F(12')-C(38')-C(37') 120.4(4)

C(39')-C(38')-C(37') 119.6(4)

F(13')-C(39')-C(38') 120.4(4)

F(13')-C(39')-C(40') 121.1(4)

C(38')-C(39')-C(40') 118.5(4)

F(14')-C(40')-C(39') 119.8(4)

F(14')-C(40')-C(41') 120.2(4)

C(39')-C(40')-C(41') 120.0(4)

F(15')-C(41')-C(40') 115.1(3)

F(15')-C(41')-C(36') 120.8(4)

C(40')-C(41')-C(36') 124.2(4)

C(43')-C(42')-C(47') 112.7(4)

C(43')-C(42')-B(1') 121.0(4)

C(47')-C(42')-B(1') 125.7(4)

95


______________________________________________________________________________

F(16')-C(43')-C(44') 116.1(4)

F(16')-C(43')-C(42') 118.4(3)

C(44')-C(43')-C(42') 125.5(4)

F(17')-C(44')-C(43') 121.3(4)

F(17')-C(44')-C(45') 118.9(4)

C(43')-C(44')-C(45') 119.8(4)

F(18')-C(45')-C(44') 121.2(4)

F(18')-C(45')-C(46') 121.6(4)

C(44')-C(45')-C(46') 117.3(4)

F(19')-C(46')-C(47') 120.1(4)

F(19')-C(46')-C(45') 118.6(4)

C(47')-C(46')-C(45') 121.3(4)

F(20')-C(47')-C(46') 115.9(4)

F(20')-C(47')-C(42') 120.8(4)

C(46')-C(47')-C(42') 123.4(4)

_____________________________________________________________________________

96

Figure 2.24. Synthesis of di-1-adamantylphosphinic chloride

Synthesis of di-1-adamantylphosphinic chloride113 (2.28) In a 2 L pear shaped flask

equipped with magnetic stirring bar and distilling column, a mixture of adamantane

(54.8782 g, 0.403 mol), aluminum (III) chloride (61.9397 g, 0.464 mol), and of

phosphorus (III) chloride (180 mL, 2.06 mol) was refluxed for 7 h under positive nitrogen

atmosphere. Then the excess of phosphorus (III) chloride was distilled off until about 150

mL liquid had been collected, leaving a viscous substance residue. After cooling to room

temperature, dichloromethane (350 mL) was added to reaction flask and the flask cooled

in an ice-water bath. The resulting suspension was cautiously hydrolyzed with ice-water

mixture (~250 mL) and stirred overnight at 0 oC. White sticky solid separated out of the

mixture overnight leaving an orange suspension on top. Vacuum filtration of the mixture

resulted in two immiscible liquid layers, where the upper organic layer was separated and

dried over MgSO4. After filtration, removal of solvents from the filtrate using a rotary

evaporator and drying in a desiccator under oil pump vacuum overnight resulted in

mostly white solid in 97.4 % yield (69.2311 g). 1H NMR (400 MHz, chloroform-d) δ

1.74 (broad s, 12H), 2.04 (broad s, 6H), 2.14 (broad s, 12H). 31P NMR (162 MHz,

chloroform-d) δ 85.8 (s) ppm.

97

Figure 2.25. Synthesis of di-1-adamantylphosphine

Synthesis of di-1-adamantylphosphine113 (2.29) In a 2 L pear shaped flask equipped

with magnetic stirring bar, di-1-adamantylphosphinic chloride (21.2345 g, 60.2 mmol)

was dissolved in freshly distilled THF (300 mL) and flask was cooled in an ice-water

bath while stirring the solution under nitrogen atmosphere. Lithium aluminum hydride

(5.7471 g, 151.4 mmol) was added in 1 g portions over 90 min. After warming to room

temperature overnight, the reaction mixture was cooled to 0 oC in an ice-water bath, and

hydrolyzed with 16 mL H2O:THF mixture (6 + 10 mL) followed by 3 M NaOH (12 mL)

and DI-H2O (18 mL). After stirring for 5 h, the suspension was vacuum filtered and

filtrate was reduced to half volume using a rotary evaporator. White solid separated out

and was vacuum filtered and dried in a desiccator over phosphorus pentaoxide, under oil

pump vacuum, leaving the product as white solid (14.3864 g, 79.1 % yield) 1H NMR

(500 MHz, chloroform-d) δ 1.72 (broad s, 12H), 1.89 (broad s, 6H), 1.94 (broad s, 12H),

2.79 (d, J = 200, 1H). 31P NMR (202 MHz, chloroform-d) δ 17.8 (s) ppm.

Figure 2.26. Synthesis of di-1-adamantylchlorophosphine

98

Synthesis of di-1-adamantylchlorophosphine113 (2.30) In a 500 mL Schlenk flask

equipped with magnetic stirring bar, di-1-adamantylphosphine (4.0951 g, 13.5 mmol) and

1,8-diazabicyclo[5.4.0]undec-7-ene, DBU, (2.41 g, 15.8 mmol) was dissolved in dry and

deoxygenated toluene (300 mL) and the flask was cooled to 0 oC in ice-water bath under

nitrogen atmosphere. Phosgene in toluene (12 mL of 20 % solution, 2.2 g, 22.6 mmol

phosgene) was added over 15 min via gas tight syringe through the septum. The color of

the solution turned pale yellow with white solid (presumed DBU.HCl) formation.

Reaction progress was monitored using 31P NMR spectroscopic analysis of aliquots over

4 h and nitrogen gas was bubbled through to ensure removal of excess phosgene. After

vacuum filtration in glovebox, solvents were removed in vacuo at 25-30 oC on a Schlenk

line outside the glovebox. The resulting white chalky solid was washed with hexanes and

dried under oil pump vacuum, leaving white solid (3.58 g, 79.2 % yield). 1H NMR (400

MHz, dry chloroform-d) δ 2.0-1.6 (m, 30H). 31P NMR (202 MHz, chloroform-d) δ 139.9

(s) ppm.

Figure 2.27. Synthesis of 4-(tert-butyl)-2-(di-1-adamatylphosphino)-1-methyl-1H-imidazole

4-(tert-butyl)-2-(di-1-adamatylphosphino)-1-methyl-1H-imidazole (2.31). In a

Schlenk flask equipped with magnetic stirbar, 4-(tert-butyl)-1-methyl-1H-imidazole

99

(207.5 mg, 1.501 mmol) was dissolved in dry and deoxygenated THF (30 mL) and the

flask was placed in an acetonitrile-Dry Ice bath intended to be at -30 °C. Using a syringe,

nBuLi in hexanes (620 µL of 2.5 M, 1.53 mmol) was added to the reaction dropwise over

30 min. After 1 h, di-1-adamantylchlorophosphine (505.3 mg, 1.5 mmol) solution in dry

and deoxygenated THF (30 mL) was added dropwise using syringes over 15 min. After

addition was complete, the reaction was allowed to warm to room temperature and heated

in oil bath at 50 oC for 4 h and 62 oC for 2.5 h while aliquots taken from the reaction were

analyzed using 1H and 31P NMR spectroscopy. After the reaction stirred at room

temperature overnight, it was quenched by adding deoxygenated methanol (0.5 mL).

Solvents were removed on a vacuum line and the 107.7 mg of the resulting off-white

solid was recrystallized from aqueous ethanol. Pure compound was obtained as a white

solid (59.6 mg, 0.14 mmol, 55.3 % yield ). 1H NMR (500 MHz, acetone-d6) δ 1.30 (s,

9H), 1.74-1.64 (m, 12H), 1.86-1.76 (m, 6H), 1.92-1.86 (m, 6H), 2.24-2.14 (m, 6H), 3.76

(s, 3H), 6.85 (d, J = 3.0, 1 H) ppm. 31P NMR (202 MHz, acetone-d6) δ 1.8 (s) ppm.

Elemental calculated for C23H39N2P (438.63) C, 76.67; H, 9.88; N, 6.39.

Figure 2.28. Synthesis of 2.21

100

Synthesis of [CpRu (4-(tert-butyl)-2-(di-1-adamantylphosphino)-1-methyl-1H-

imidazole)(acetonitrile)]PF6 (2.21) In a glove box, ruthenium precursor

[CpRu(CH3CN)3]PF6 (5.2 mg, 0.011 mmol) was combined in a Schlenk flask equipped

with a magnetic stir bar and dry, deoxygenated THF (~0.5 mL). The phosphine 4-(tert-

butyl)-2-(di-1-adamantylphosphino)-1-methyl-1H-imidazole (5.1 mg, 0.011 mmol) was

added dropwise in dry, deoxygenated THF (0.5 mL), and the resulting solution was

allowed to stir overnight at room temperature. The solvent was removed in vacuo,

without stirring, and the residue left under vacuum until a flaky powder remained. The

product was obtained as yellow colored powder (10.6 mg, 2 mol% bis-acetonitrile

complex present, 101.9 % yield). 1H NMR (500 MHz, acetone-d6) δ 1.41 (s, 9 H), 1.86-

1.70 (m, 12H), 2.32-2.00 (m, 18H), 2.44 (s, 3 H), 3.92 (s, 3 H), 4.63 (s, 5 H), 7.06 (s, 1

H) ppm. 31P NMR (202 MHz, acetone-d6) δ 52.05 (s) ppm.

Figure 2.29. Synthesis of 4-(1-adamantyl)-2-(di-iso-propylphosphino)-1-methyl-1H-imidazole

4-(1-adamantyl)-2-(di-iso-propylphosphino)-1-methyl-1H-imidazole (2.32). In a

Schlenk flask equipped with magnetic stirbar, 4-(1-adamantyl)-1-methyl-1H-imidazole


flask was placed in an water-ice bath. Using a syringe, nBuLi in hexanes (650 µL of 2.5

101

M, 1.6 mmol) was added to the reaction dropwise over 20 min. After 2 h, di-iso-

propylchlorophosphine (246.5 mg, 1.615 mmol) was added dropwise using a gas tight

syringe over 30 min. The reaction was allowed to warm to room temperature overnight

and was quenched with deoxygenated methanol (0.8 mL) until solution became clear

(yellow-brown). Solvents were removed on a vacuum line and the resulting solid was

suspended in hexanes and the mixture filtered in the glovebox through a Celite plug. Pure

compound was obtained after passing the crude product through a silica plug, eluting

with hexanes/ethylacetate containing triethyl amine; after concentration and storage of

the residue under Teflon diaphram pump, product was obtained as yellow clear liquid

(314.9 mg, 0.95 mmol, 61.9 % yield ). 1H NMR (500 MHz, acetone-d6) δ 0.71 (dd, J =

7.0, 12.0, 6H), 0.82 (dd, J = 7.0, 15.5, 6H), 1.67-1.61 (m, 6H), 1.78-1.72 (m, 3H), 1.90-

1.82 (m, 3H), 2.25 (sep of d, J = 1.5, 7.0, 2 H), 3.52 (s, 3 H), 6.55 (s, 1 H) ppm. 31P NMR

(202 MHz, acetone-d6) δ -18.42 (s) ppm. Elemental calculated for C20H33N2P (684.64) C,

72.25; H, 10.00; N, 8.43. Found C, 71.94; H, 9.85; N, 7.96.


Complexation of 2.32 to give [CpRu (4-(1-adamantyl)-2-(di-iso-propylphosphino)-1-


102







yellow colored powder (243.9 mg, acetonitrile is present, 100.2% yield). 1H NMR (500

MHz, acetone-d6) δ 1.09 (dd, J = 7.0, 16.0, 3H), 1.19 (dd, J = 7.5, 16.5, 3H), 1.36 (dd, J =

7.0, 18.0, 3H), 1.49 (dd, J = 7.0, 17.5, 3H), 2.19-2.10 (m, 6H), 2.00-1.95 (m, 3H), 1.88-

1.80 (m, 6H), 2.47 (s, 3 H), 2.85-2.78 (m, 1 H), 3.03-3.10 (m, 1H), 3.82 (s, 3 H), 4.62 (s,

5 H), 6.96 (s, 1 H) ppm. 31P NMR (202 MHz, acetone-d6) δ 37.62 (s) ppm. Elemental

calculated for C27H41F6N3P2Ru (684.64) C, 47.37; H, 6.04; N, 6.14. Found C, 46.96; H,

5.83; N, 6.30.

Figure 2.31. Synthesis of 4-(1-adamantyl)-2-(di-tert-butylphosphino)-1-methyl-1H-imidazole

4-(1-adamantyl)-2-(di-tert-butylphosphino)-1-methyl-1H-imidazole (2.33). In a

Schlenk flask equipped with magnetic stirbar, 4-(1-adamantyl)-1-methyl-1H-imidazole


flask was placed in an acetone-Dry Ice bath at -78 °C. Using a syringe, nBuLi in hexanes

103

(580 µL of 2.5 M, 1.42 mmol) was added to the reaction dropwise over 15 min. After 2 h,

di-tert-butylchlorophosphine (317.0 mg, 1.75 mmol) was added dropwise using a gas

tight syringe over 25 min. The reaction was allowed to warm to room temperature and

was quenched with deoxygenated methanol until solution became clear and orange.

Solvents were removed on a vacuum line and the resulting solid was suspended in

hexanes and the mixture filtered in the glovebox through Celite. Column chromatography

with hexanes and ethyl acetate (5:1) containing triethyl amine yielded pure compound

was obtained as a yellow sticky solid (320.1 mg, 0.89 mmol, 64 % yield). 1H NMR (500

MHz, acetone-d6) δ 1.18 (d, J = 12.0, 18H), 1.84-1.72 (m, 6H), 1.94-1.90 (m, 6H), 2.02-

1.98 (m, 3H), 3.79 (s, 3 H), 6.81 (s, 1 H) ppm. 31P NMR (202 MHz, acetone-d6) δ 1.23 (s)

ppm. Elemental calculated for C22H37N2P (360.52) C, 73.29; H, 10.34; N, 7.77. Found C,

72.90; H, 9.96; N, 7.53.


Complexation of 2.33 to give [CpRu (4-(1-adamantyl)-2-(di-tert-butylphosphino)-1-





104




yellow-orange colored powder (368.1 mg, acetone is present, 103.3% yield). 1H NMR

(500 MHz, acetone-d6) δ 1.48 (broad d, J = 11.0, 18H), 1.90-1.82 (m, 6H), 2.20-2.10 (m,

6H), 2.50-2.32 (m, 3H), 2.69 (s, 3 H), 3.90 (s, 3 H), 4.62 (s, 5 H), 7.02 (s, 1 H) ppm. 31P

NMR (202 MHz, acetone-d6) δ 58.71 (s) ppm. Elemental calculated for C29H45F6N3P2Ru

(712.70) C, 48.87; H, 6.36; N, 5.90. Found C, 48.24; H, 6.20; N, 5.49.

General procedure for catalytic isomerization reactions of 1-heptene

In a glove box, internal standard (Me3Si)4C (small weighed amount) and substrate (0.50

mmol) were combined with acetone-d6 (~700 µL), and an initial NMR spectrum was

acquired. Back in the glovebox, to this mixture was added catalyst 2.10, 2.19-2.23 (0.01

mmol; 2 mol%) followed by enough acetone-d6 to reach a final volume of 1.0 mL. If the

mixture was heated at 70 oC in an oil bath it was done so for the times given, spectra were

acquired at NMR probe temperature of 30 oC. The value of the integral for the singlet due

to the internal standard, C(Me3Si)4, was set equal to 100.00 integral units in each case.

Data were acquired with eight 15o pulses and 20 sec delays between pulses.

1-heptene isomerization with 2.10 at room temperature. (Table 2.15) General

procedure was followed using 1-heptene (49.1 mg, 0.50 mmol), C(Me3Si)4 (0.9 mg, 2.9

µmol) and 2.10 (6.1 mg, 0.01 mmol) in acetone-d6 (1 mL).

105

Table 2.15. 1-heptene Isomerization with 2 mol % 2.10 in NMR probe

Time (min) 1-Heptene (%) 2-Heptene (%) 3-Heptene (%)

15 1.4 67.7 28.5

24 1.2 59.5 36.9

32 1.1 55.7 40.8

40 1.2 54.1 42.5

50 0.9 52.5 44.2

60 1.1 52.3 44.8

65 1.2 52.3 44.7

70 1.0 51.6 44.6

75 1.1 51.9 44.9

80 1.1 51.5 45.3

90 1.0 51.2 45.3




Table 2.16. 1-heptene Isomerization with 2 mol % 2.19 at RT

Time (h) 1-Heptene (%) 2-Heptene (%) 3-Heptene (%)

1 1.4 60.1 37.3

2 1.5 53.7 44.3

5 0.9 51.9 45.5

24 1.1 52.8 45.0

106




Table 2.17. 1-heptene Isomerization with 2 mol % 2.19 in NMR probe


5 1.7 86.3 11.5

10 1.3 82.5 14.5

15 1.2 60.1 36.5

30 1.2 57.5 41.3

60 0.6 52.0 46.6

90 1.0 51.2 46.9

120 1.1 51.3 46.5




Table 2.18. 1-heptene Isomerization with 2 mol % 2.20 at RT

Time (h) 1-Heptene (%) 2-Heptene (%) 3-Heptene (%)

1 96.6 0.6 -

10 93.4 2.1 <1

24 3.1 4.6 <1

1-heptene isomerization with 2.20 70 oC. (Table 2.19) General procedure was followed

using 1-heptene (49.3 mg, 0.50 mmol), C(Me3Si)4 (1.7 mg, 5.6 µmol) and 2.20 (6.4 mg,

0.01 mmol) in acetone-d6 (1 mL) and the J. Young NMR tube was placed in an oil bath at

70 oC.

107

Table 2.19. 1-heptene isomerization with 2 mol % 2.20 at 70 oC

Time 1-Heptene (%) 2-Heptene (%) (E:Z) 3-Heptene (%)

20 min 94.3 5.3 - <1

40 min 88.7 11.5 - <1

1 h 82.6 17.7 9.7 : 1 <1

1.5 h 73.6 25.1 10.8 : 1 1.4

2 h 62.4 34.1 11 : 1 1.7

11 h 8.6 84.3 6.6 : 1 7.7

23 h 3.5 85.1 6.0 : 1 11.3

1-heptene isomerization with 2.21 at 70 oC. (Table 2.20) General procedure was

followed using 1-heptene (63.7 mg, 0.66 mmol), C(Me3Si)4 (1.5 mg, 4.9 µmol) and 2.21

(10.5 mg, 0.0132 mmol) in acetone-d6 (1.4 mL) and placed the J. Young NMR tube in oil

bath at 70 oC.



20 min 43.6 52.1 9.5 : 1 3.2

40 min 5.9 81.1 9 : 1 12.5

1 h 2.6 79.9 8.6 : 1 17.6

1.5 h 1.9 78.1 6.8 : 1 20.6

2 h 1.8 76.8 6.7 : 1 21.5

3 h 1.7 77.1 6 : 1 22.2

11 h 1.5 76.0 4.6 : 1 23.1

23 h 1.6 76.3 4 : 1 22.9

35 h 1.6 76.0 3.9 :1 23.4

108




Table 2.21. 1-heptene isomerization with 2 mol % 2.22 at RT


9 1.6 79.0 17.8

12 1.5 75.4 22.0

28 1.2 62.8 34.7

32 1.1 59.9 38.9

37 1.2 58.2 39.6

50 1.2 55.3 43.0

60 1.1 54.7 43.9

70 1.1 53.5 44.2

80 1.2 53.0 45.2

92 1.3 52.5 45.8




Table 2.22. 1-heptene isomerization with 2 mol % 2.23 at RT ge715

Time (h) 1-Heptene (%) 2-Heptene (%) (E : Z) 3-Heptene (%)

1 97.6 1.3 - -

10 95.2 1.5 - -

24 86.3 11.6 5.3 : 1 <1

1-heptene isomerization with 2.23 at 70 oC. (Table 2.21) General procedure was

followed using 1-heptene (49.8 mg, 0.51 mmol), C(Me3Si)4 (1.8 mg, 5.9 µmol) and 2.23

109

(7.0 mg, 0.01 mmol) in acetone-d6 (1 mL) and placed the J. Young NMR tube in oil bath

at 70 oC.


Time (h) 1-Heptene (%) 2-Heptene (%) (E:Z) 3-Heptene (%)

1 h 2.8 78.8 10 : 1 15.4

14 h 1.8 76.7 6.2 : 1 21.5

36 h 1.3 75.9 4.1 : 1 22.4

1-heptene isomerization with 2.23 at 70 oC (repeat with spectra taken at shorter

intervals). (Table 2.21) General procedure was followed using 1-heptene (49.3 mg, 0.50

mmol), C(Me3Si)4 (1.7 mg, 5.6 µmol) and 2.23 (6.4 mg, 0.01 mmol) in acetone-d6 (1 mL)

and placed the J. Young NMR tube in oil bath at 70 oC.



20 min 11.4 79.0 9.7 : 1 10.0

40 min 4.3 81.9 9.4 : 1 15.0

60 min 2.6 79.7 9.1 :1 17.0

90 min 2.7 79.7 9.3 :1 18.5

2 h 2.2 78.9 8.4 :1 19.4

11h 1.8 77.3 5.8 : 1 22.1

23 h 1.8 76.0 6.1 : 1 22.2

1-hexene isomerization with 2.20 at room temperature. (Table 2.25 entry 1, 2)

General procedure used for 1-heptene was followed using 1-hexene (25.3 mg, 0.50

mmol), C(Me3Si)4 (3.3 mg, 5.6 µmol) and 2.20 (3.8 mg, µmol) in acetone-d6 (1 mL).

110

1-hexene isomerization with 2.20 at 70 oC. (Table 2.25, entry 3) General procedure

used for 1-heptene was followed using 1-hexene (28.6 mg, 0.34 mmol), 1,4-dioxane as

internal standard (9.9 mg, 0.11 mmol) and 2.20 (4.3 mg, 6.8 µmol) in acetone-d6 (1 mL)

and placed the J. Young NMR tube in oil bath at 70 oC.

Table 2.25. 1-hexene isomerization with 2 mol % 2.20 at RT and 70 oC

Time (h) 1-Hexene (%) 2-Hexene (%) 3-Hexene (%)

24, RT 100 - -

66, RT 92.8 7.0 <1

24, 70 oC 18.3 70.0 6.0

1-decene isomerization with 2.20 at 70 oC. (Table 2.26) General procedure used for 1-

heptene was followed using 1-decene (28.8 mg, 0.20 mmol), C(Me3Si)4 (1.1 mg, 3.6

µmol) and 2.20 (2.5 mg, 4.2 µmol) in acetone-d6 (1 mL) and placed the J. Young NMR

tube in oil bath at 70 oC.

Table 2.26. 1-decene isomerization with 2 mol % 2.20 at 70 oC

Time (h) 1-decene (%) 2-decene (%) 3- and 4-decene

(%)

1 90.5 6.2 <1

5 81.4 15.4 <1

36 49.6 44.8 4

48 43.1 49.5 10

1-hexene isomerization with 2.23 at 70 oC. (Table 2.27) General procedure used for 1-

heptene was followed using 1-hexene (12.6 mg, 0.15 mmol), C(Me3Si)4 (0.9 mg, 2.9

111

µmol) and 2.23 (2.1 mg, µmol) in acetone-d6 (1 mL) and placed the J. Young NMR tube

in oil bath at 70 oC.

Table 2.27. 1-hexene isomerization with 2 mol % 2.23 at RT

Time (min) 1-Hexene (%) 2-Hexene (%) 3-Hexene (%)

7 94.3 6.2 <1

45 71.3 26.0 2.4

65 51.9 41.9 4.0

90 31.9 58.7 7.6

123 14.0 68.3 11.1

150 2.0 72.1 20.5

180 1.5 68.0 23.5

42 h 1.7 61.2 22.7

112

The part of the contents of Chapter 2 are similar to the material published in the

following papers: Grotjahn, Douglas B.; Larsen, Casey; Erdogan, Gulin; Gustafson,

Jeffrey; Sharma, Abhinandini; Nair, Reji. “Bifunctional catalysis of alkene isomerization

and its applications” Chemical Industries (Boca Raton, FL, United States) 2009, 123,

379-387. Grotjahn, Douglas B; Larsen, Casey, R; Gustafson, Jeffery, L; Nair, Reji;

Sharma, Abhinandini. “Extensive isomerization of alkenes using a bifunctional catalyst:

an alkene zipper”. Journal of the American Chemical Society 2007, 129, 9592-9593. The

dissertation author was the primary researcher for the data presented and co-author on the

papers included. The co-authors listed in these publications also participated in the

research.

113

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120

CHAPTER 3

POLYMER SUPPORTED ALKENE

ISOMERIZATION

121

INTRODUCTION

Despite the significant advantages of homogeneous catalysis, which include high

efficiency and high selectivity, there is still demand for highly active and stable

heterogeneous systems due to the tedious and time-consuming purification steps required

to remove homogeneous catalysts from reaction mixtures. In organometallic catalysis,

where both the product and the catalyst’s ligands are small organic molecules,

chromatography often represents the best purification option. Here, immobilization of the

catalyst may provide an elegant solution to purification problems.1 Immobilized catalysts

can provide faster synthetic procedures, reduce costs, and promote environmentally

friendly industrial manufacturing.2 Fine chemicals production and pharmaceuticals

production provide high value commodities from building blocks to drugs that allow us

to support the ever-expanding world. Production of these materials require high

selectivity in terms of chemo-, regio- and stereo- selectivity which can be provided by

homogenous catalysts but separation and purification are among the biggest hindrances to

commercialization. Thus, the motivating factors for creating selective yet recoverable

catalysts are large.

Homogeneous catalysts provide greater selectivity and controllability due to their

molecular nature ensuring the presence of only a single type of active site, whereas

heterogeneous catalysts may contain ill-defined surfaces that lead to difficult design and

improvement. On the other hand, the inherent difficulty and expense of separating a

homogeneous catalyst from the products at the end of the reaction along with easier

handling and robust nature of heterogeneous catalysts has often led industry to prefer use

122

of the latter. An ideal catalyst, therefore, would be one that is: (1) readily separated from

the stream of reactants and products, (2) able to be recycled without losing efficiency, (3)

equivalent to or better than the best homogeneous catalyst and (4) specific for the desired

reaction.1,3 An immobilized molecular catalyst on an insoluble support could function

mechanistically as if in solution and at the same time offer all the engineering and

manipulative advantages of heterogeneous catalysts.

The great variety of catalyst solid supports1,3,4 can be divided into two broad

classes, (1) inorganic oxides, and (2) organic polymers. Typical examples of both are

listed in Table 3.1. Both exhibit contrasting advantages and disadvantages. One of the

most important differences is the degree to which they can be functionalized; organic

matrices can be loaded up to 10 meq/g but inorganic matrices cannot be loaded to an

extent more than 1-2 meq/g of matrix.5

Inorganic supports are superior in thermal and mechanical stability but they lack

the chemical stability, inertness and flexibility. They are more resilient to changes in

temperature, pressure and solvent polarity compared to organic supports.

Table 3.1. Supports for immobilization

Organic Inorganic

Polystyrene Silica

Polyamide Alumina

Polymethacrylate Zeolite

Polybutadiene Clay

Polyvinyl Carbon

Silicone resins Metal oxides

123

The principle advantages of organic polymers are (1) easy modification and

functionalization, (2) controllable physical properties, and (3) chemical inertness (except

at higher temperatures). Although organic polymers have poor mechanical stability that

prevent their use in stirred reactions, this can be overcome by introducing techniques that

prevent pulverization. The porous nature of polymers offers the advantage of higher

selectivity through control of diffusion, but at the same time the rate of the reaction

depends on the accessibility of the catalytic sites within the polymer. The choice of

solvent along with temperature can highly affect the swelling, and therefore change the

pore size and govern the size of molecules and at which rate they can reach or leave the

active sites.

In the work described below, 2% cross-linked polystyrene was chosen as the

support for the alkene isomerization catalyst. Since the introduction of the Merrifield

resin for peptide synthesis, cross-linked polystyrene-supported catalysts have been

adopted for numerous organic reactions to facilitate product purification and catalyst

recovery.6-8 Functionalization of the preformed commercial polymer is practical and can

be well adapted from previous literature. For example, Pericas and coworkers reported

immobilization of (E)-4-hydroxyproline onto Merrifield-type polymers through a copper-

mediated 1,3-dipolar cycloaddition.9

124

Figure 3.1. Immobilization of (E)-4-hydroxyproline

The immobilized proline-derived catalyst in Figure 3.1 can be used (Figure 3.2)

for diastereoselective direct aldol reactions, enantioselective alpha-aminoxylation of

aldehydes and ketones,10 and asymmetric Manninch reaction of aldehydes with

preformed N-(p-methoxyphenyl)ethyl glyoxylate imine. 11

125

Figure 3.2. Reactions catalyzed by polystyrene immobilized (E)-4-hydroxyprline. (a) Diasteroselective direct aldol reactions, (b) Enantioselective alpha-aminoxylation of ketones, (c) Enantioselective Mannich reactions

Metathesis catalysts have received great attention and several attempts to

immobilize them on different types of supports have been published. Grela et al. reported

immobilizing 2nd generation Hoveyda-Grubbs catalyst on PS-DES (Figure 3.3), which is

commercially available and easily accessed by treating Merrifield resin with

allylmagnesiumchloride followed by hydrosilylation with diethylsilane.12

Figure 3.3. PS-DES synthesis from Merrifield resin

126

Polymer-supported 2nd generation Hoveyda-Grubbs catalyst (3.4, Figure 3.4) was

successfully recycled up to six cycles without significant loss of activity, and the same

batch of recycled catalyst could be used sequentially in different metathesis reactions. 13

Figure 3.4. Polymer-supported 2nd generation Hoveyda-Grubbs metathesis catalyst

There are different strategies to bind a catalyst to a support; immobilization of

proline-derived catalyst is an example of direct immobilization where the pre-built ligand

or complex is anchored on the support (Figure 3.1). The approach followed for

immobilization of metathesis catalyst (Figure 3.4) is an example of stepwise synthesis

where the ligands and complex is added to the polymer in a stepwise fashion. Although

the direct immobilization of a preformed metal complex is advantageous because it

127

reduces the possibility of non-selective metal binding, an alternative strategy involving

the stepwise synthesis of ligands on the solid support has the advantage of being able to

prepare libraries. Starting with an anchored ligand, different metal complexes can be

formed leading greater versatility. When using stepwise solid phase synthesis approach,

the characterization of the species formed on the solid support can be hard to characterize

and the undesired coordination of the metal to the support along with incomplete ligand

formation and complexation should be kept in mind. On the other hand excess reagents

ad other products can be removed from the immobilized complex by thorough washes

with appropriate solvents.

As mentioned in chapter 3, isomerization of carbon-carbon double bonds is a

desirable reaction. Significantly, our search of the literature on heterogeneous14-23 or

heterogenized24-32 alkene isomerization catalysts revealed a lack of highly selective

systems. Some heterogeneous alkene isomerization systems use strong acid15,18,20 or base

16,17 catalytic sites. Many of the systems require high temperatures and they either suffer

from forming positional isomers14-23,25,29 in thermodynamic ratios and/or mixtures of

geometric isomers.14-31 Heterogeneous systems that use metals3 as active components

provide milder conditions and among these, perhaps the best system is reported by Ley et

al. in synthesis of the natural product carpapone, using a polymer-supported form of

Felkin’s iridium catalyst with (E)-olefin selectivity up to >98%.

128

Figure 3.5. Polymer-supported Felkin’s iridium catalyst

The isomerization reactions were carried out with about 40 mol% catalytic

loading for 24 h at room temperature. Electron-rich arylated allylic systems were

successfully isomerized in highly (E)-selective fashion, whereas, with electron poor

systems only up to 50% isomerization was possible. Allyl ether isomerizations took place

with high conversions but essentially equimolar mixtures of (Z)- and (E)-products were

obtained. Regardless of the type of the substrate, up to 4% of the hydrogenated alkene

product was present. Also worthy to note that when compared to the homogenous system,

the polymer-supported system was reported to be less geometrically selective.31,32 In

summary; (1) immobilized Felkin’s iridium catalyst requires catalyst activation with H2

gas prior to use, (2) polymer-supported system is less (E)-selective than the related

homogenous catalyst, (3) small amount of hydrogenation products are observed along

with minor or equivalent amount of (Z)-products in several substrates, (4) use of up to 40

mol % catalytic loadings are used.

129

Table 3.2. Scope of polymer-supported Felkin’s iridium catalyst

Starting Material Product (E)-(Z) Selectivity

(E) only

~92% (E)

1 :1

Mixture of (E) and (Z)

50% Conversion -

Recovered starting material with

<4% isomerized product -

Recovered starting material -

130

DESIGN, DEVELOPMENT AND TESTING OF HETEROGENIZED CATALYSTS

Previously reported systems for alkene isomerization lack the high selectivity for

(E)-isomers and best system reported so far suffers from loss of (E)-selectivity upon

immobilization. Homogenous alkene isomerization catalyst (chapter 3) reported in the

Grotjahn group shows exceptional ability to move double bonds over many positions

with functional group tolerance and geometric selectivity towards (E)-alkenes regardless

of functional group present. For example, silyl ethers where the (Z)-isomers are

thermodynamically stable versus unfunctionalized hydrocarbon chains where (E)-isomers

are more stable.33 Immobilization of alkene isomerization catalyst 2.10 in the form of

began by on Merrifield resin by the sodium salt of 4-(tert-butyl)-1H-imidazole for PS-1

followed by installation of phosphine functionality using nBuLi, then iPr2PCl and finally

complexation employing [CpRu(CH3CN)3]PF6 as precursor. The point of attachment to

the resin was chosen as N1 on the pendant base, which is proposed on the basis of X-ray

diffraction studies to be away from the active site of the catalyst.34

131

Figure 3.6. Synthesis of polymer-supported alkene isomerization catalyst PS-1

In order to explore the effects of having the active site further away from the resin

matrix with possibly improved substrate and product transport rates,35,36 in addition to

PS-1 a second version of the catalyst (PSL-1, Figure 3.7) featuring a tether of five atoms

was also envisioned. The longer tether was installed by alkylation of the sodium salt of 4-

tBu-imidazole using tetrahydropyran-protected 3-bromopropanol, followed by

deprotection of the THP ether to reveal the alcohol. The displacement of chloride on

Merrifield resin was accomplished by the alkoxide accessed from deprotonation of 3.9

with sodium hydride. Installation of phosphine functionality and complexation was as

followed in PS-1. Polymer was extensively washed at each step and composition of the

polymer was determined by elemental analysis via nitrogen percent weight.

132

Figure 3.7. Synthesis of polymer-supported alkene isomerization catalyst PSL-1

Compared to their homogenous counterparts, in general, heterogeneous catalysts

are generally harder to characterize. Polymer was extensively washed at each step and

composition of the polymer was determined by elemental analysis via nitrogen percent

weight, but this technique could give direct evidence of ligand or catalyst structure. In

order to verify full complexation of [CpRu(CH3CN)3]PF6 with polystyrene supported 4-

tert-butyl-2-(diisopropylphosphino)-1H-imidazole and absence of free phosphine, a

smaller scale reaction of PS-1 was carried out in a J. Young NMR tube. 31P NMR data

for PS-2 shows a single peak at -18.7 ppm, which is in agreement with data for the

solution-phase imidazolylphosphine (-18.5 ppm in acetone-d6). Metal complexation was

carried out with 1 equivalent of ruthenium precursor [CpRu(CH3CN)3]PF6 and the

133

absence of the peak at -18.7 ppm confirmed that complexation was complete, and the

chemical shift of 41.5 ppm suggests that on the resin, PS-1 was present rather than PS-2.

The ligands in PSL-1 and PS-1 appear to be the first polymer-supported

imidazolylphosphines.

Isomerization of alkene substrates was achieved at low (1-2 mol %) catalyst

loadings in acetone as solvent, either at room temperature or at 70 °C. At room

temperature, reactions were performed in vials with Teflon-lined caps that were placed

on a nutator in order to introduce mixing without mechanical destruction of the polymer

beads. Reactions at elevated temperatures were conducted in resealable J. Young NMR

tubes without mechanical mixing of any kind; further optimization of mixing technique

during heating might lead to improved results. The performance of heterogenized

catalysts PS-1 and PSL-1 was compared with that of soluble catalyst 1 by subjecting

substrates to similar conditions and observing the progress of isomerization by 1H NMR

spectroscopy.

134

Table 3.3. Substrate scope of PS-1 and PSL-1

Entry Starting

Material Product Catalyst

Mol

% T(oC) Time

Yield

%

1

PS-1

PSL-1

2.10

2

2

2

RT

RT

RT

20 min

20 min

10 min

96.3

98.6

99.2

2

PS-1

PSL-1

2.10

2

2

2

RT

RT

RT

30 min

30 min

4 min

97.1

96.5

99.8

3

PS-1

PSL-1

2.10

5

5

5

70

70

70

24 h

24 h

4 h

70.5

57.7

90

4

PS-1

PSL-1

2.10

2

2

2

70

70

70

48 h

72 h

1 h

91.2

83.9

98.0

5

PS-1

PSL-1

2.10

2

2

2

RT

RT

RT

5 h

5 h

40 min

97.4

98.6

96

6

PS-1

PSL-1

2.10

2

2

2

70

70

70

2 h

1 h

1 h

91.2

90.0

97.0

7

PS-1

PSL-1

2.10

2

2

2

70

70

70

1 h

23 h

45 min

78.1

81.8

91.6

8

PS-1

PSL-1

2.10

1

1

1

RT

RT

RT

45 min

52 min

4 min

98.5

94.4

98.8

Isomerization of 4-allyl anisole, eugenol and diallyl ether was achieved at room

temperature (Table 3.3). In each case performance of PS-1 and PSL-1 was comparable,

135

where both catalysts retained the very high stereoselectivty of solution phase catalyst

2.10 to yield (E)-isomers. PS-1 outperformed PSL-1 with substrates that require either

multiple bond movements or are sterically more challenging.

Solvent-free reactions lead to new environmentally benign procedures that save

resources and energy. They reduce the burden of organic solvent disposal and also bring

down handling costs by simplifying experimental procedure and work up techniques

consequently help saving costs during industrial production.37 Our attempt to circumvent

use of organic solvents lead us to the observation of reversal of the relative performances

of PS-1 and PSL-1, though both effective (Figure 3.8). In general, under neat conditions,

PSL-1 isomerizes 4-penten-2-ol, eugenol and 2-allylcyclohexanone in shorter time than

does PS-1. Isomerization of 4-penten-2-ol was carried out with 2 mol% catalyst at room

temperature. In two hours, PSL-1 produces 90.7 % of corresponding ketone where as PS-

1 reaches same amount of ketone in 5 hours. It is worth noting that in 2 h, PS-1 yields

19.9 % ketone and only 27.6 % starting alcohol is left, whereas the rest of the reaction

mixture contains internal olefins. Eugenol and allylcyclohexanone were isomerized using

1 mol% catalytic loading. Quantitative conversion to (E)-isoeugenol was possible over 24

h, although the reactions were possibly complete before this time.

136

Figure 3.8. Isomerizations with PS-1 and PSL-1 under neat conditions

To further highlight the advantages of an immobilized alkene isomerization

catalyst, alkene isomerization and metathesis have been performed in sequence without

purification along the way. Stilbenoids, especially resveratrol, have received attention

due to their potential value in cancer prevention and therapy38-40 and they are shown to be

accessible by metathesis.38 Therefore, 4-allyl anisole and TMS-protected eugenol were

isomerized with PS-1. After filtration, isomerized alkenes were subjected to metathesis

reaction with silica-supported 2nd generation Hoveyda-Grubbs catalyst that was prepared

according to literature.41 Metathesis products were isolated in 73.5 and 87 % overall

yield, respectively.

137

Figure 3.9. Sequential polymer-supported alkene isomerization and silica-supported metathesis

Alkenyl aromatics, like 4-allyl anisole, eugenol and their isomers are used in a

wide range of flavoring, cosmetic, fragrance and pharmaceutical applications. Isoeugenol

is extracted from natural sources or traditionally generated from eugenol by isomerization

using stoichiometric excess KOH in alcoholic solutions at high temperature (200 °C).42

Recycling and recovery studies were carried out with PS-1 in the isomerization of

eugenol to E-isoeugenol because of commercial interest in obtaining the product free of

(Z)-isomer, as well as free of metal residues. The ruthenium content of combined filtrates

and washes from each cycle was determined by inductively coupled plasma optical

emission spectroscopy (ICP-OES) analysis.43-45 The substrate conversion during each of

the five cycles is near quantitative and yet in total only about 1.3 % ruthenium of the

initial loading is lost, with 0.7% being lost in the first cycle. The higher leaching at the

first cycle suggests the presence of more loosely held ruthenium species, perhaps

138

deposited in the pores of the polymer. In order to reduce metal contamination further,

pre-treatment of the polymer-supported catalysts may further reduce the amount of metal

leached into product.

Table 3.4. Recycling experiments performed with PS-1 and amount of metal leaching

Cycle # % Eugenol % (E)-Isoeugenol Ru concentration

(ppm)

1 0.6 98.1 1.08

2 0.9 99.4 0.51

3 0.3 99.9 0.17

4 0.2 98.4 0.11

5 0.2 97.1 0.07

In conclusion, we find it significant that the very high kinetic selectivity for

formation of (E)-isomers is completely retained on heterogenization. In general, both PS-

2.10 and PSL-1 show lower but still very useful activity compared to that of 2.10,

probably due to slow diffusion rates, which is a common trait for heterogenized catalysts.

Compared to their homogenous counterparts, in general, heterogeneous catalysts are

generally harder to characterize and suffer from slower diffusion rates and lower

activity.1,46 PSL-1 outperforms PS-1 under neat conditions. The difference in activity

may be attributed to easier access to PSL-1 active site provided by the longer tethering.

Faster isomerization with PSL-1 of the neat liquid substrates examined may also due to

this catalyst’s ability to swell faster compared to PS-1 with substrates containing

functionalities with oxygen. Overall, 1 is successfully heterogenized as PS-1 and PSL-1;

139

the selectivity of the catalyst is fully retained with very low metal leaching from the

insoluble support. Ongoing work seeks to create faster heterogeneous bifunctional

catalysts for a variety of applications.

DESIGN, DEVELOPMENT AND TESTING OF SOLUBLE HETEROGENIZED CATALYSTS

Polymeric supports had become a driving force for lab automation and separation

techniques. Increasing number of new polymeric supports have been published and used

for supported catalysis. Every polymer has its drawbacks and advantages hence can be

utilized for the parameters they offer. As an alternative to insoluble polymeric supports,

soluble polymer supports can be used to immobilize catalysts. Soluble supports will

allow overcoming disadvantages such as difficult analysis of catalyst composition, or

substrate access to active sites. By having the supported catalyst soluble in the reaction

medium, the catalyst, in theory, will behave more like its homogenous analogue and will

allow for better selectivity, yield and especially reaction rate.47

140

Figure 3.10. Examples of soluble polymers

Changing the temperature and/or polarity profile of the reaction can facilitate

precipitation and enable recycling and recovery of a soluble polymer supported catalyst

by simple filtration. Polyethyleneglycol (PEG), polyethylene (PE), and linear atactic

polystyrenes (aPS) have been widely used as soluble polymer supports. PEG and PE

suffer from low loading capacities due to their end-functionalized nature. Attempts to

overcome these limitations by branching result in reduced solubility. Linear polystyrenes

with low cross linking often times require demanding filtration techniques due their poor

precipitation properties.48 Syndiotactic polystyrene49 (sPS) is a crystalline material that

can be recovered in high yields because of the high stereoregular nature of the main

chain. Also various loading capacities can be achieved by changing the functional group

levels in the side chain of the polymer just like on any other polystyrene resin.

Bae et al. have demonstrated functionalization of sPS controlled functionalization

of sPS through iridium-catalyzed borylation via activation of aromatic C-H bonds in the

side chains up to 42 mol% incorporation of pinacolboronate ester (B(pin)) group.50

141

Quantitative recovery of pinacolboronate ester-functionalized sPS (sPS-B(pin)) as a fine

powder has been achieved by adding an equal volume of methanol to a 5 mL chloroform

solution of 50 mg sPS-B(pin). Under the same conditions, aPS-B(pin) recovery was only

55%, and as a sticky solid.

Figure 3.11. Borylation of sPS with Ir-catalyzed C-H activation

Boronate esters are versatile intermediates used in organic synthesis. sPS-B(pin)

can be further functionalized, for example, a hydroxyl group can be introduced by

oxidation of the ester and through Suzuki-Miyaura cross-coupling different functional

groups can be introduced onto sPS. Bae et al. successfully used triphenylphosphine-

functionalized sPS (sPS-TPP) in Suzuki-Miyaura coupling of both electron-rich and

electron-poor aryl halides. Simple precipitation of the sPS-TPP-supported palladium

catalyst was again achieved by methanol recycled over four cycles without loss of

activity. Over five cycles sPS-TPP-supported palladium catalyst was recovered

quantitatively.51

142

Figure 3.12. Facile functionalization of sPS-B(pin)

Taking this study as precedent, we decided to support alkene isomerization

catalyst on sPS. Considering our previous approach to immobilization, we decided the

point of attachment to the resin as N1 on the pendant base, using a benzyl spacer by

means of Suzuki-Miyaura coupling conditions. Addition of the phosphine functionality

and metal complexation should take place in similar reaction conditions to PS-1 and

PSL-1. Different reaction conditions were investigated to establish whether the benzyl

spacer can be installed at the desired position with the tertiary butyl group still at the 4-

position (Figure 3.13, compound 3.12). Due to electron delocalization between N1 and

N3, the benzylation reaction can occur adjacent to the more hindered nitrogen (3.13). Use

143

of 1-bromo-4-(chloromethyl)benzene with N-methyl-2-pyrrolidone (NMP) as solvent at -

18 oC are the optimal conditions for the best product distribution(Table 3.5).

Figure 3.13. Benzyl spacer installment on 4-(tBu)-imidazole

Table 3.5. Reaction conditions for optimal 1-(4-bromobenzyl)-4-(tBu)-imidazole synthesis

Leaving

Group

Ratio of Electrophile

to Imidazole Solvent

Temperature

(oC)

Product Ratio

(3.12 : 3.13)

Br 1 : 1 THF 0 100 :20

Br 1 : 1 THF 25 100 : 18

Br 1 : 1 DMF 0 100 : 10

Br 1 : 1 NMP 0 100 : 8

Br 1 : 0.8 DMF -42 100 : 8

Cl 1 : 0.8 NMP -18 100 : 3

Cl 1 : 0.8 DMF -42 100 : 5

A sample of sPS (from Dow Chemicals and Prof. Gaetano Guerra,

Dipartimento di Chimica Università di Salerno Via Ponte Don Melillo) with molecular

weight 3.2 x 105 g/mol was functionalized according to literature50 using chloro(1,5-

cyclooctadiene)iridium(I) dimer, [IrCl(COD)]2, with 4,4’-di-tert-butyl-2,2’-bipyridine as

base and bis(pinacolato)diboron as borylating agent in cyclooctane. The amount of B(pin)

groups incorporated on the side chains was calculated from ratios of the 1H NMR

144

(obtained in chloroform-d) integrals of the methine peaks from the main chain versus the

those of the methyl groups of B(pin). According to these calculations, 1.5 to 2.7 % B(pin)

incorporation was achieved by using 3% Ir and different amounts of B2(pin)2. Before

installation of the imidazole on the sPS, the reaction of sPS-B(pin) was tried with

bromotoluene as a model. Observance of 1H NMR peaks around 2.4 ppm suggested that

the sPS-B(pin) had been arylated under the reaction conditions.

Figure 3.14. Synthesis of sPS-B(pin) and 1H NMR signals used to calculate % incorporation

The incorporation of bromotoluene was successful, when sPS(Bpin) was coupled

with 1-(4-bromobenzyl)-4-tert-Bu-imidazole under the same conditions, diastereotopic

hydrogens of the methylene spacer as a singlet were observed around 5.0 ppm in the 1H

NMR spectrum. Changing the base from NMe4OH to NEt4OH or NaOtBu didn’t improve

the reaction.

145

Figure 3.15. Functionalization of sPS-B(pin)

Treatment of 3.15 with BuLi in THF resulted in color change from light yellow to

dark yellow. In comparison, the color change at this step starting with PS-1 and PSL-1

was from yellow to deep red color with the addition of BuLi and generation of the

nucleophile, which faded back to yellow upon treatment with chlorophosphine. 3.16 was

obtained as a gray solid, where NMR spectroscopic analysis of a solution in chloroform-d

showed 31P NMR peaks at -2.2, -50. 7, and -99.1 ppm, and in the 1H NMR spectrum, and

an identifiable signal for the diastereotopic hydrogens of the methylene spacer were not

observed between 4.8 and 5.2 ppm. Multiple signals seen in the 31P NMR spectra

suggested that there was more than one phosphine species formed, where perhaps even

deprotonation and phosphination of the methylene spacer had taken place. Attempt to

complex this sample with [CpRu(CH3)3]PF6 was not successful.

146

Figure 3.16. Synthesis of sPS-1

147


Figure 3.17. Synthesis of polystyrene-supported 4-tert-butyl-1-1H-imidazole

Polystyrene-supported 4-tert-butyl-1H-imidazole (3.5): The resin used, Merrifield HL

(50-100 mesh) was purchased from Novabiochem and the concentration of reactive

chloromethyl groups was assayed by the supplier as 1.1 mmol per gram. In a nitrogen-

filled glovebox, using a scintillation vial, NaH (97.1 mg, 2.43 mmol, 60% by weight in

mineral oil) was washed with dry hexanes and dried under reduced pressure. A solution

of 4-tert-butyl-1H-imidazole (251.7 mg, 2.03 mmol) in dry NMP (5 mL) was added to

NaH. The resulting mixture was stirred for 10 min before the reaction mixture was

transferred to a vial containing Merrifield resin (1.0044 g, 1.10 mmol) swelled with dry

NMP (~5 mL). The mixture was slowly stirred in a 50 oC oil bath overnight. The reaction

mixture was transferred to a polyethylene syringe equipped with fritted disk and Teflon

valve. The liquid was expelled and the resin was rinsed with dry NMP (total of 20 mL in

three portions). The resin was washed with methanol (10 mL) then alternating between

dichloromethane (10 mL) and methanol, four times each. The resin was stirred with

dichloromethane in the syringe overnight before draining the liquid and drying the resin

under reduced pressure for ~ 4 days (1.1005 g 99.9 %). Elemental analysis Calculated: N,

2.81; Found: C, 88.41; H, 8.23; N, 3.14.

148

Figure 3.18. Synthesis of 4-tert-butyl-2-(diisopropylphosphino)-1H-imidazole

Polystyrene-supported 4-tert-butyl-2-(diisopropylphosphino)-1H-imidazole (3.6): In

a nitrogen-filled glovebox, using a polyethylene syringe equipped with fritted disk and

Teflon valve, dry THF (~3 mL) was added to polystyrene supported 4-tert-butyl-2-

(diisopropylphosphino)-1H-imidazole (314.6 mg, 379.4 µmol). After 5 h BuLi (325 µL,

1.52 M in hexanes, 494 µmol) was added dropwise. The resin turned cherry red almost

immediately. After 10 min of stirring, liquids were expelled and the resin was washed

with dry THF (3 x 3 mL). A solution of ClP(i-Pr2)2 (69.2 mg, 453 µmol) in dry THF (~1

mL) was added and color of the resin faded to yellow almost immediately. After 2 h of

stirring the liquids were expelled and the resin was washed with dry THF (4 x 5 mL). The

syringe assembly was placed in a desiccator under reduced pressure for 3 d (395.6 g

118.1 %). Elemental analysis Calculated: N 2.52; Found: C, 85.58; H, 8.21; N, 2.70.

149

Figure 3.19. Synthesis of PS-1

Polystyrene-supported 2.10 (PS-1): In a nitrogen-filled glovebox, using a polyethylene

syringe equipped with fritted disk and Teflon valve, polystyrene-supported 3-(4-tert-

butyl-2-(diisopropylphosphino)-1H-imidazole (359.0 mg, 322.4 µmol) was swelled with

acetone (~2 mL). A solution of [CpRu(CH3CN)3]PF6 (307.8 mg, 609.4 µmol) in acetone

(~4 mL) was added to syringe containing the resin. After stirring for 1 h, liquids were

expelled and the resin was washed with acetone (6 x 4 mL). The syringe assembly was

placed in a desiccator under reduced pressure for 3 d (456.3 g 96.6 %). Elemental

analysis Calculated: N, 2.87; Found: C, 68.37; H, 6.63; N, 2.59.

150

Figure 3.20. 31P NMR spectrum of PS-2 (left) and PS-1 (right)

J. Young scale PS-1 synthesis for NMR analysis was performed in order to verify full

complexation of [CpRu(CH3CN)3]PF6 with polystyrene supported 4-tert-butyl-2-

(diisopropylphosphino)-1H-imidazole and absence of free phosphine. A J. Young NMR

tube was charged with polystyrene supported 4-tert-butyl-1H-imidazole (115.5 mg, 0.116

mmol), and dry and deoxygenated THF was added until the resin was all wet. A portion

of BuLi solution (50.0 µL, 2.5M in hexanes, 0.116 mmol) was added to a 1-dram vial and

diluted with THF (0.5 mL). The resulting solution was quantitatively transferred into the

J. Young NMR tube dropwise. The color changed from light yellow to cherry red, similar

to that observed in a larger-scale reaction (see above). The reaction was left to proceed at

room temperature for 1.5 h. A solution of ClP(i-Pr2)2 (17.6 mg, 0.116 mmol) in dry THF

151

was added to the tube quantitative using portions of THF. The color of the resin faded to

yellow almost immediately. The J. Young NMR tube was placed on a nutator for reaction

to proceed at room temperature for 9 h.

A 31P NMR spectrum52 was acquired and a single peak at -18.7 ppm was observed with

respect to an external 85 % H3PO4(aq) capillary placed in the tube. This chemical shift is

analogous to that of the free imidazolylphosphine 3.6 (-18.5 ppm in acetone-d6).

Figure 3.21. Synthesis of 2-(3-bromopropoxy)tetrahydro-2H-pyran

2-(3-bromopropoxy)tetrahydro-2H-pyran (3.7): In a round bottom flask, a solution of

3-bromopropanol (2.1093 g, 15.2 mmol) and 3,4-dihydro-2H-pyran (1.9118 g, 22.7

mmol) in dichloromethane (30 mL) containing p-toluenesulfonic acid mono hydrate

(291.0 mg, 1.53 mmol) was stirred overnight at room temperature. The solution was

diluted with hexanes and washed with DI H2O (total of 250 mL in four portions). The

aqueous layer was back-extracted with hexanes (2 X 50 mL). Combined organic layers

were dried with anhydrous MgSO4, filtered, and after removing the solvents under

reduced pressure the crude product was purified by column chromatography over silica,

eluting with 4:1 hexanes:diethyl ether, to give the product (3.0269 g, 97.4 %) as a an oil.

1H NMR (500 MHz, chloroform-d) δ 4.62-4.59 (m, 1H), 3.89-3.85 (m, 2H), 3.56-3.51

(m, 4H), 2.17-2.13 (m, 2H), 1.84-1.66 (m, 2H), 1.60-1.52 (m, 4H). Data are in

accordance with those previously reported.53,54

152

Figure 3.22. Synthesis of 4-tert-butyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-

imidazole

4-tert-butyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-imidazole (3.8): In a

nitrogen-filled glovebox, using a Schlenk flask NaH (711.2mg, 17.8 mmol, 60% by

weight in mineral oil) was washed with dry hexanes and dried under reduced pressure. In

a vial 4-tert-butyl-1H-imidazole (1.8159 g, 14.6 mmol) was dissolved in NMP (5 mL)

and the resulting solution transferred to Schlenk flask, which was taken out of the

glovebox and connected to a Schlenk line and placed in an ice-water bath. After stirring

overnight at room temperature, reaction mixture was diluted with DI H2O and washed

with Et2O (4 x 50 mL). Combined organic layers were washed with DI H2O (2 x 50 mL)

and dried over anhydrous MgSO4. After filtration and removing the solvents under

reduced pressure, the residue was purified by column chromatography over silica, eluting

with 1:4 hexanes:ethyl acetate, to give the product (3.4433 g, 94.1 %). 1H NMR (500

MHz, chloroform-d) δ 7.39 (d, J = 1.0 Hz, 1H), 6.63 (d, J = 1.5 Hz, 1H), 4.55-4.54 (m,

1H), 4.05-3.96 (m, 2H), (ddd, J = 3.5, 4.0, 11.0 Hz, 1H), 3.87-3.83 (m, 1H), 3.79-3.75

(dt, J = 5.5, 10.0 Hz, 1H), 3.53-3.50 (m, 1H), 3.39-3.33 (td, J = 6.0, 10.0 Hz, 1H), 2.06-

2.01 (dquin, J = 1.0, 6.0 Hz, 2H), 1.86-1.82 (m, 1H), 1.76-1.71 (m, 1H), 1.62-1.52 (m,

4H), 1.29 (s, 9H).

153

Elemental analysis Calculated: C, 67.63; H, 9.84; N, 10.52. Found: C, 64.26; H, 9.81; N,

10.09.

Figure 3.23. 3-(4-tert-butyl-1H-imidazol-1-yl)propan-1-ol

3-(4-tert-butyl-1H-imidazol-1-yl)propan-1-ol (3.9):4 In a round bottom flask, a solution

of 4-tert-butyl-1-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1H-imidazole (3.3008 g, 12.4

mmol) in methanol (700 mL) containing p-toluenesulfonic acid monohydrate (4.7633 g,

25.0 mmol) was stirred overnight at room temperature. The reaction mixture was

quenched with solid NaOH and concentrated under reduced pressure. The residue was

dissolved in DI H2O and washed with diethyl ether until washings showed no TL spots

visible above the origin when eluted with 1:4 hexanes:ethyl acetate. Combined organic

layers were washed with brine (2 x 50 mL) and dried with anhydrous MgSO4. After

filtration, the solvents were removed under reduced pressure to give the product (2.0064

g, 88.8 %) as a yellow solid. 1H NMR (500 MHz, chloroform-d) δ 7.40 (d, J = 1.5 Hz,

1H), 6.62 (d, J = 1.5 Hz, 1H), 4.03 (t, J = 7.0 Hz, 1H), 3.65 (t, J = 6.0 Hz, 2H), 2.10-1.99

(m, 2H), 1.29 (s, 9H).

Elemental analysis Calculated: C, 65.90; H, 9.95; N, 15.37. Found: C, 65.66; H, 9.98; N,

15.09.

154

Figure 3.24. Polystyrene-supprted 4-tert-butyl-1H-imidazol-1-yl group with linker

Polystyrene-supported 4-tert-butyl-1H-imidazol-1-yl group with linker (3.10): The

resin used, Merrifield HL (50-100 mesh) was purchased from Novabiochem and the

concentration of reactive chloromethyl groups was assayed by the supplier as 1.1 mmol

per gram. In a nitrogen-filled glovebox, using a scintillation vial, NaH (121.3 mg, 3.0

mmol, 60% by weight in mineral oil) was washed with dry hexanes and dried under

reduced pressure. A solution of 3-(4-tert-butyl-1H-imidazol-1-yl) propan-1-ol (546.4 mg,

3.00 mmol) in NMP (2 mL) was added to the NaH, and the resulting mixture was stirred

for 10 min before being transferred to a vial containing Merrifield resin (1.4870 g, 1.64

mmol) swelled with NMP (~5 mL). The mixture was slowly stirred in a 50 oC oil bath

overnight. The reaction mixture was transferred to a polyethylene syringe equipped with

fritted disk and Teflon valve. The liquid was expelled and the resin was rinsed with dry

NMP (total of 20 mL in three portions). The resin was washed with methanol (10 mL)

then alternating between dichloromethane (10 mL) and methanol, four times each. The

resin was stirred with dichloromethane in the syringe overnight before draining the liquid

and drying the resin under reduced pressure with oil-pump vacuum for ~ 8 d (1.5678 g

96.9 %). Elemental analysis Calculated: N, 2.65. Found: C, 87.45; H, 8.61; N, 2.73.

155

Figure 3.25. Polystyrene-supported 4-tert-butyl-2-(diisopropylphosphino-1H-imidazole

Polystyrene-supported 4-tert-butyl-2-(diisopropylphosphino)-1H-imidazole ligand

with linker (3.11): In a nitrogen-filled glovebox, using a polyethylene syringe equipped

with fritted disk and Teflon, dry THF (~3 mL) was added to polystyrene supported 3-(4-

tert-butyl-1H-imidazol-1-yl)propan-1-ol (400.0 mg, 0.38 mmol). After 5 h, BuLi solution

(380 µL, 1.52 M in hexanes, 578 µmol) was added dropwise. The resin turned cherry red

almost immediately. After 10 min of stirring, liquids were expelled and resin was

washed with dry THF (3 x 3 mL). A solution of ClP(i-Pr2)2 (87.9 mg, 576 µmol) in dry

THF (~1 mL) was added and color of the resin faded to yellow almost immediately. After

2 h of stirring the liquids were expelled and the resin was washed with dry THF (4 x 5

mL). The syringe assembly was placed in a desiccator under reduced pressure with oil-

pump vacuum for 3 d (467.0 mg 105.2 %). Elemental analysis Calculated: N, 2.39.

Found: C, 85.19; H, 8.03; N, 2.25.

156

Figure 3.26. Synthesis of PSL-1

Polystyrene-supported 2.10 with linker (PSL-1): In a nitrogen-filled glovebox, using a

polyethylene syringe equipped with fritted disk and Teflon, polystyrene supported 3-(4-

tert-butyl-2-(diisopropylphosphino)-1H-imidazol-1-yl)propan-1-ol (443.0 mg, 371.1

µmol) was swelled with acetone (~2 mL). A solution of CpRu(CH3CN)3PF6 (226.6 mg,

448.7 µmol) in acetone (~4 mL) was added to the syringe containing the resin. After

stirring for 1 h, liquids were expelled and resin was washed with acetone (6 x 5 mL). The

syringe assembly was placed in a desiccator under reduced pressure with oil-pump

vacuum for 3 d (573.8 mg 100.0 %). Elemental analysis Calculated N 2.72 Found: C,

68.67; H, 6.61; N, 2.38.

157

General procedures for catalytic isomerization reactions

General Procedure A: In the glovebox, polymer-supported catalyst was weighed in a

conical vial and acetone-d6 is added to swell the polymer supported catalyst. In a separate

vial, substrate was weighed and tetrakis(trimethylsilyl)methane or 1,4-dioxane was added

as internal standard. Acetone-d6 was added to ensure complete dissolution of all material.

A small sample (<3 µL) was removed by capillary action into the tip of a Pasteur pipette

and the sample was analyzed in acetone-d6 to get an initial 1H NMR spectrum to set the

integral values. A solution of substrate and internal standard was added to the conical

vial. The substrate vial was washed with additional acetone-d6 and washings were added

to the conical vial. The reaction mixture was stirred with a magnetic stir bar at room

temperature. The progress of the reaction was monitored by stopping the stirring briefly

and removing a sample by a Pasteur pipette tip from the reaction mixture. Samples were

analyzed by 1H NMR.

General Procedure B: Reactions were set up as in General Procedure A, except that

either a conical vial or a J. Young NMR tube was used for the reaction. In addition,

during the reaction, rather than stirring, a nutator was used to agitate the mixture gently.

In the cases where a J. Young NMR tube was used as reaction vessel, NMR spectra could

be acquired directly, without the need to remove aliquots.

General Procedure C: Reactions were set up as in General Procedure A, except, the

conical vial was immersed in an oil bath at 70oC and the reaction was stirred with a

magnetic stirrer.

158

General Procedure D: Reactions were set up as in General Procedure A, except that

either a conical vial or a J. Young NMR tube was used for the reaction. The conical vial

or J. Young NMR tube was immersed in an oil bath at 70 oC. In the cases where a J.

Young NMR tube was used as reaction vessel, NMR spectra could be acquired directly,

without the need to remove aliquots.

Figure 3.27. Isomerization of 4-allylanisole

Isomerization of 4-allylanisole with PS-1. General procedure B was followed using 4-

allylanisole (74.0 mg, 0.50 mmol), PS-1 (14.7 mg, 0.010 mmol, 2 mol %) and

tetrakis(trimethylsilyl)methane (1.5 mg, 4.92 x 10-3 mmol). Starting material 1H NMR

(500 MHz, acetone-d6) δ 7.10 (~d, AA’ of AA’BB’, J = 8.8 Hz, 2H), 6.85 (~d, BB’ of

AA’BB’, J = 8.8 Hz, 2H), 5.94 (tdd, J = 6.8, 10.0, 16.8 Hz, 1H), 5.05 (tdd, J = 1.6, 2.0,

17.2 Hz, 1H), 5.00 (tdd, J = 1.2, 2.0, 10.0 Hz, 1H), 3.76 (s, 3H), 3.31 (d, J = 6.8 Hz, 2H).

Product (E)-Anethole 1H NMR at 96 h (500 MHz, acetone-d6) δ 7.29 (~d, AA’ of

AA’BB’, J = 9.2 Hz, 2H), 6.85 (~d, BB’ of AA’BB’, J = 8.8 Hz, 2H), 6.37-6.34 (m, 1H),

6.10 (bs, 1H), 3.77 (s, 3H), 1.80-1.75 (m, 2H).

Table 3.6. Isomerization of 4-allylanisole with PS-1

Time (min) Starting material (%) Product (%)

2 78.7 25.7

5 51.5 46.5

10 21.5 78.6

20 - 96.3

159

Isomerization of 4-allylanisole with PSL-1. General procedure B was followed using 4-

allylanisole (74.1 mg, 0.50 mmol), PSL-1 (15.5 mg, 0.010 mmol, 2 mol %) and

tetrakis(trimethylsilyl)methane (1.3 mg, 4.26 x 10-3 mmol).

Table 3.7. Isomerization of 4-allylanisole with PSL-1


2 76.5 20.6

5 49.9 44.7

10 19.1 80.9

20 - 98.6

Isomerization of 4-allylanisole with 2.10. A J. Young NMR tube was charged with

tetrakis(trimethylsilyl)methane (1.2 mg), 4-allyl anisole (22.5 mg, 0.15 mmol), in

acetone-d6 (about 0.8 mL). After acquisition of an initial spectrum to set the integral

values, 2.10 (1.8 mg, 3.0 x 10-3 mmol, 2 mol %) was transferred quantitatively from a

vial using acetone-d6 in several portions into the J. Young NMR tube. Total reaction

volume was adjusted to 1 mL by addition of acetone-d6.

Table 3.8. Isomerization of 4-allylanisole with 2.10


10 - 99.2

Figure 3.28. Isomerization of allyloxy(tert-butyl)dimethylsilane

160

Isomerization of allyloxy(tert-butyl)dimethylsilane with PS-1. General procedure B

was followed using allyloxy(tert-butyl)dimethylsilane (87.4 mg, 0.51 mmol), PS-1 (14.7

mg, 0.010 mmol, 2 mol %) and tetrakis(trimethylsilyl)methane (1.6 mg, 5.25 x 10-3

mmol). Starting material 1H NMR (500 MHz, acetone-d6) δ 5.92 (tdd, J = 4.4, 10.4,

17.2, 1H), 5.26 (tdd, J = 2.0, 2.0, 17.2, 1H), 5.04 (tdd, J = 1.6, 1.6, 10.4, 1H), (ddd, J =

1.4, 2.0, 4.4, 2H), 0.91 (s, 9H), 0.07 (s, 6H) Product 1H NMR (500 MHz, acetone-d6) δ

6.29 (qd, J = 1.7, 11.9, 1H), 4.94 (qd, J = 6.8, 11.8, 1H), 1.48 (dd, J = 1.6, 6.8, 3H), 0.91

(s, 9H), 0.12 (s, 6H).

Table 3.9. Isomerization of allyloxy(tert-butyl)dimethylsilane with PS-1


20 19.7 80.5

30 3.7 97.0

40 <1 97.1

Isomerization of allyloxy(tert-butyl)dimethylsilane with PSL-1. General procedure B

was followed using allyloxy(tert-butyl)dimethylsilane (87.3 mg, 0.51 mmol), PSL-1

(15.5 mg, 0.010 mmol, 2 mol %) and tetrakis(trimethylsilyl)methane (1.5 mg, 4.92 x 10-3

mmol).

161

Table 3.10. Isomerization of allyloxyallyloxy(tert-butyl)dimethylsilane with PSL-1


20 14.4 80.9

30 1.2 96.5

40 <1 97.3

Isomerization of allyloxy(tert-butyl)dimethylsilane with 2.10. A J. Young NMR tube

was charged with tetrakis(trimethylsilyl)methane (1.0 mg, 3.28 x 10-3 mmol) and

allyloxy(tert-butyl)dimethylsilane (26.1 mg, 0.15 mmol) in acetone-d6 . After acquisition

of an initial spectrum to set the integral values, 2.10 (1.9 mg, 3.1 x 10-3 mmol, 2 mol %)

was transferred quantitatively from a vial using acetone-d6 in several portions into the J.

Young NMR tube. Total reaction volume was adjusted to 1.2 mL by addition of acetone-

d6.

Table 3.11. Isomerization of allyloxy(tert-butyl)dimethylsilane with 2.10

Time (min) Starting material (%) Isomer (%)

4 0.5 99.8

Figure 3.29. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane

Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 5 mol% PS-1.

General procedure D was followed using tert-butyldimethyl(pent-4-enyloxy)silane (100.2

mg, 0.50 mmol), PS-1 (36.6 mg, 0.025 mmol, 5 mol %) and

162

tetrakis(trimethylsilyl)methane (2.5 mg, 8.20 x 10-3 mmol). Starting material 1H NMR

(500 MHz, acetone-d6) δ 5.84 (tdd, J = 7.0, 10.0, 17.0, 1H), 4.99 (tdd, J = 1.5, 2.0, 17.0,

1H), 4.92 (tdd, J = 1.0, 2.5, 9.0, 1H), 3.64 (t, J = 6.0, 2H) 2.11 (~tdd, 4JH1-H3 = 2.0 Hz,

3JH2-H3 = 3JH3-H4 = 7.4, 2H), 1.59 (tt, 3JH4-H5 = 6.5 3JH3-H4 = 7.5, 2H), 0.90 (s, 9H), 0.05 (s,

6H). Product 1H NMR (500 MHz, acetone-d6) δ 6.29 (td, J = 1.5, 12.0, 1H), 4.94 (td, J =

7.5, 12.0, 1H), 1.86 (qd, J = 1.0, 7.2, 2H), 1.33 (td, J = 7.5, 14.5, 2H), 0.92 (s, 9H), 0.87

(t, J = 7.5, 3H), 0.13 (s, 6H).

Table 3.12. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 5 mol% PS-1

Time (h) Starting material (%) 2- and 3-alkenes (%) Enol ether (%)

2 7.0 63.4 19.9

5 1.5 50.0 37.8

15 <1 31.3 64.5

24 <1 15.4 70.5

Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 5 mol% PSL-1.

General procedure D was followed using tert-butyldimethyl(pent-4-enyloxy)silane (102.2

mg, 0.50 mmol), PSL-1 (38.6 mg, 0.025 mmol, 5 mol %) and


163

Table 3.13. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 5 mol% PSL-1

Time (h) Starting material (%) 2- and 3-alkenes (%) Enol ether (%)

1 36.9 54.3 7.0

2 13.6 63.1 13.1

5 14.4 63.1 12.9

15 <1 38.4 46.8

24 <1 25.5 57.7

Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 2 mol% PS-1.

General procedure D was followed in a J. Young NMR tube using tert-

butyldimethyl(pent-4-enyloxy)silane (30.8 mg, 0.15 mmol), PS-1 (4.6 mg, 3.0 x 10-3

mmol, 2 mol %) and 1,4-dioxane (9.7 mg, 0.11 mmol).

Table 3.14. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 2 mol% PS-1

Time (h) Starting material (%) 2-alkene (%) 3-alkene (%) Enol ether (%)

1 13.0 72.5 9.5 8.7

2 9.0 74.6 11.5 15.1

5 3.9 61.4 10.2 28.8

24 1.9 33.8 2.6 60.2

48 0.7 19.2 3.4 71.0

164

Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with PSL-1. General

procedure D was followed in a J. Young NMR tube using tert-butyldimethyl(pent-4-

enyloxy)silane (33.5 mg, 0.17 mmol), PSL-1 (5.2 mg, 3.4 x 10-3 mmol, 2 mol %) and

1,4-dioxane (8.8 mg, 0.099 mmol).

Table 3.15. Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 2 mol% PSL-1

Time (h) Starting material (%) 2-alkene (%) 3-alkene (%) Enol ether (%)

1 47.0 46.4 4.8 1.3

2 25.4 61.1 7.2 9.1

5 11.1 68.7 9.5 16.4

24 2.8 56.7 9.4 33.8

48 1.6 38.0 6.9 51.7

Isomerization of tert-butyldimethyl(pent-4-enyloxy)silane with 2.10 as seen in

reference 29 Table 1 entry 8.

Figure 3.30. Isomerization of methylenecyclohexane

Isomerization of methylenecyclohexane with PS-1. General procedure D was followed

using methylenecyclohexane (19.2 mg, 0.20 mmol), PS-1 (5.8 mg, 4.0x10-3 mmol, 2 mol

%) and 1,4-dioxane (10.6 mg, 0.12 mmol). Starting material 1H NMR (500 MHz,

acetone-d6) δ 4.56 (t, J = 1 Hz, 2H), 2.09-2.12 (br m, 4H), 1.53 ppm (br s, 6H). 1-methyl-

cyclohexene in the mixture: 1H NMR (500 MHz, acetone-d6) δ 5.36 (qd, J = 2.0, 3.0,

165

1H), 1.96-1.91 (m, J = 2, 2H), 1.86-1.90 (br m, 2H), 1.57-1.62 (m, 5H), 1.49-1.55 ppm

(m, 2H).

Table 3.16. Isomerization of methylenecyclohexane with PS-1

Time (h) Starting material (%) Isomer (%)

1 86.7 12.0

2 75.5 23.3

5 55.3 42.2

24 16.7 79.6

48 6.4 91.2

72 3.3 93.9

Isomerization of methylenecyclohexane with PSL-1. General procedure D was

followed using methylenecyclohexane (19.7 mg, 0.21 mmol), PSL-1 (6.2 mg, 4.0 x 10-3

mmol, 2 mol %) and tetrakis(trimethylsilyl)methane (10.3 mg, 0.12 mmol).

Table 3.17. Isomerization of methylenecyclohexane with PSL-1


1 87.7 10.6

2 78.6 19.0

5 65.0 32.3

24 33.2 62.2

48 16.3 78.6

72 9.8 83.9

166

Isomerization of methylenecyclohexane with 2.10. A J. Young NMR tube was charged

with tetrakis(trimethylsilyl)methane (1.1 mg, 3.61 x 10-3 mmol) and

methylenecyclohexane (20.9 mg, 0.22 mmol) in acetone-d6 (about 1 mL). After

acquisition of an initial spectrum to set the integral values, 2.10 (2.6 mg, 4.3 x 10-3 mmol,

2 mol %) was transferred quantitatively from a vial using acetone-d6 in several portions

into the J. Young NMR tube. Total reaction volume was adjusted to ca. 1.2 mL by

addition of acetone-d6.

Table 3.18. Isomerization of methylenecyclohexane with 2.10


1 2.4 98.0

2 1.1 99.2

Figure 3.31. Isomerization of allyl ether

Isomerization of allyl ether with PS-1. General procedure A was followed using allyl

ether (50.3 mg, 0.51 mmol), 1,4-dioxane (10.9 mg, 0.12 mmol), and PS-1 (14.7 mg,

0.010 mmol, 2 mol%). Starting material 1H NMR (400 MHz, acetone-d6) δ 5.91 (tdd, J

= 3.2, 12.8, 17.6 Hz, 2H), 5.27 (qd, J = 1.8, 17.2 Hz, 2H), 5.13 (qd, J = 1.4, 10.4 Hz, 2H),

3.97 (td, J = 1.6, 6.2 Hz, 4H). Intermediate 1H NMR (400 MHz, acetone-d6) δ 6.26 (dq,

J = 1.6, 12.4 Hz, 1H), 5.31 (dq, J = 1.8, 17.4 Hz, 1H), 5.30 (tdd, J = 6.2, 10.4, 17.2 Hz,

1H), 5.17 (dq, J = 1.6, 10.4 Hz, 1H), 4.79 (dq, J = 6.8, 12.8 Hz, 1H), 4.18 (dt, J = 1.6, 5.2

167

Hz, 2H), 1.52 (dd, J = 1.6, 6.8 Hz, 3H). Product 1H NMR (400 MHz, acetone-d6) δ 6.32

(dq, J = 1.6, 12.2 Hz, 2H), 5.02 (dq, J = 6.8, 12.4 Hz, 2H), 1.55 (dd, J = 1.6, 6.8 Hz, 6H).

Table 3.19. Isomerization of allyl ether with PS-1

Time (h) Starting material (%) Intermediate (%) Product (%)

1 1.2 46.7 53.1

2 - 17.9 79.8

5 - - 97.4

Isomerization of allyl ether with PSL-1. General procedure A was followed using allyl

ether (50.3 mg, 0.51 mmol), 1,4-dioxane (10.9 mg, 0.12 mmol), and PSL-1 (15.5 mg,

0.010 mmol, 2 mol%).

Table 3.20. Isomerization of allyl ether with PSL-1

Time (min) Starting material (%) Intermediate (%) Product (%)

1 1.5 46.2 52.4

2 - 16.7 81.8

5 - - 98.6

Isomerization of allyl ether with 2.10 as seen in reference 29 Table 1 entry 2.

Figure 3.32. Isomerization of 4-penten-2-ol

Isomerization of 4-penten-2-ol with PS-1. General procedure C was followed using 4-

penten-2-ol (86.2 mg, 1.00 mmol), PS-1 (29.4 mg, 0.020 mmol, 2 mol %) and a few

168

crystals of tetrakis(trimethylsilyl)methane. Starting material 1H NMR (400 MHz,

acetone-d6) δ 5.86 (tdd, J = 7.2, 10.0, 17.2, 1H), 5.03 (d, J = 17.5, 1H), 4.98 (d, J = 10.5,

1H), 3.76 (~ septet, J ≈ 6, 1H), 3.49 (d, J = 4.8, 1H), 2.16 (ttd, J = 1.5, 6.5, 14, 2H), 1.11

ppm (d, J = 6.4, 3H). Product 2-pentanone in mixture (400 MHz, acetone-d6) δ 2.41 (t,

J = 7.2, 2H), 2.06 (s, 3H), 1.53 (sextet, J = 7.5, 2H), 0.87 ppm (t, J = 7.5, 3H).

Table 3.21. Isomerization of 4-penten-2-ol with PS-1

Time (h) Starting material (%) Isomer (%) Ketone (%)

1 1 27 80

2 - - 91.2

Isomerization of 4-penten-2-ol with PSL-1. General procedure C was followed using 4-

penten-2-ol (86.2 mg, 1.00 mmol), PSL-1 (31.0 mg, 0.020 mmol, 2 mol %) and a few

crystals of tetrakis(trimethylsilyl)methane.

Table 3.22. Isomerization of 4-penten-2-ol with PSL-1

Time (h) Starting material (%) Isomer (%) Ketone (%)

1 1.8 2.3 90

Isomerization of 4-penten-2-ol with 2.10 as seen in reference 29, Table 1 entry 7.

Figure 3.33. Isomerization of 2-allylcyclohexanone

169

Isomerization of 2-allylcyclohexanone with PS-1. General procedure D was followed

using 2-allylcyclohexanone (29.6 mg, 0.21 mmol), PS-1 (6.2 mg, 4.2x10-3 mmol, 2 mol

%) and 1,4-dioxane (12.2 mg, 0.14 mmol). Starting material 1H NMR (500 MHz,

acetone-d6): δ 5.78 (dddd, J = 6.0, 7.5, 10.0, 18.0, 1H), 5.00 (tdd, J = 2.0, 2.5, 17.5, 1H),

4.95 (tdd, J = 1.0, 1.0, 10, 1H), 2.44-2.50 (m, 1H), 2.33-2.43 (m, 2H), 2.28 (tddd, J = 1.5,

1.5, 1.5, 13, 1H), 2.08-2.14 (m, 1H), 2.00-2.04 (m, 1H), 1.90-1.97 (m, 1H), 1.81-1.87 (m,

1H), 1.57-1.76 (m, 2H), 1.32 ppm (dtd, J = 3.5, 12.5, 13.0, 1H). 2-(prop-2-en-1-

yl)cyclohexan-1-one in the mixture: 1H NMR (500 MHz, acetone-d6) δ 5.63 (qdd, J =

1.5, 7.0, 15.5,1H), 5.42 (dqd, J = 1.5, 6.5, 19.5, 1H), 2.99-3.03 (m, 1H), 2.24-2.36 (m,

2H), 1.95-2.06 (m, 2H), 1.82-1.88 (m, 1H), 1.66-1.78 (m, H), 1.65 (qd, J = 1.0, 6.5, 3H),

1.54-1.62 ppm (m, 1H).

Table 3.23. Isomerization of 2-allylcyclohexanone with PS-1

Time (h) Starting material (%) Isomerized product (%)

1 7.5 78.1

2 7.2 75.9a

23 5.3 60.8a

48 5.0 52.9a

a Further isomerization to α-β unsaturated ketone, 2-propylidenecyclohexanone is observed.

Isomerization of 2-allylcyclohexanone with PSL-1. General procedure D was followed

using 2-allylcyclohexanone (29.4 mg, 0.21 mmol), PSL-1 (6.8 mg, 4.4 x 10-3 mmol, 2

mol %) and tetrakis(trimethylsilyl)methane (11.4 mg, 0.13 mmol).

170

Table 3.24. Isomerization of 2-allylcyclohexanone with PSL-1

Time (h) Starting material (%) Isomerized product (%)

1 40.1 51.3

2 27.0 64.2

23 7.1 81.8

48 6.1 76.8a

a Further isomerization to α-β unsaturated ketone, 2-propylidenecyclohexanone is observed. Isomerization of 2-allylcyclohexanone with 2.10. A J. Young NMR tube was charged

with tetrakis(trimethylsilyl)methane (1.3 mg, 4.26 x 10-3 mmol), 2-allylcyclohexanone

(28.2 mg, 0.20 mmol) in acetone-d6 (about 1 mL). After acquisition of an initial spectrum

to set the integral values, 2.10 (2.4 mg, 4.0 x 10-3 mmol, 2 mol %) was transferred

quantitatively from a vial using acetone-d6 in several portions into the J. Young NMR

tube. Total reaction volume was adjusted to 1.2 mL by addition of acetone-d6.

Table 3.25. Isomerization of 2-allylcyclohexanone with 2.10

Time (min) Starting material (%) Isomerized product (%)

8 38.7 60.6

20 13.8 84.3

30 7.1 90.0

45 5.8 91.6

171

Figure 3.34. Isomerization of eugenol

Isomerization of eugenol with PS-1. General procedure B was followed using eugenol

(24.8 mg, 0.15 mmol), 1,4-dioxane (5.1 mg, 0.058 mmol) and PS-1 (2.0 mg, 1.4 x 10-3

mmol, 1 mol %). Starting material eugenol 1H NMR (500 MHz, acetone-d6) δ 7.26 (s,

1H), 6.78 (d, J = 2, 2H), 6.77 (d, J = 8, 1H), 6.64 (dd, J = 1.0, 8.0, 1H), 5.95 (tdd, J = 6.5,

10.5, 17.0, 1H), 5.06 (dtd, J = 1.5, 1.5, 17.0, 1H), 4.99 (tdd, J = 1.0, 2.5, 10.0, 1H), 3.81

(s, 3H), 3.29 ppm (d, J = 7, 2H). (E)-isoeugenol in the mixture: 1H NMR (500 MHz,

acetone-d6) δ 7.43 (s, 1H), 6.99 (d, J = 2.0, 1H), 6.80 (dd, J = 2, 8, 1H), 6.74 (d, J = 8,

1H), 6.32 (dd, J = 1.5, 15.5, 1H), 6.11 (qd, J = 6.5, 15.5, 1H), 3.85 (s, 3H), 1.81 ppm (dd,

J = 2, 7, 3H).

Table 3.26. Isomerization of eugenol with PS-1


5 57.0 40.2

10 37.7 62.1

20 12.1 88.7

30 4.3 93.2

45 <1.0 98.5

Isomerization of eugenol with PSL-1. General procedure B was followed using eugenol

(25.1 mg, 0.15 mmol), 1,4-dioxane (5.2 mg, 0.059 mmol) and PSL-1 (2.3 mg, 1.5 x 10-3

mmol, 1 mol %).

172

Table 3.27. Isomerization of eugenol with PSL-1


5 69.6 23.4

10 55.7 34.7

20 32.5 62.9

30 17.8 76.5

40 8.9 87.1

52 3.2 94.4

Isomerization of eugenol with 2.10. A J. Young NMR tube was charged with

tetrakis(trimethylsilyl)methane (1.4 mg, 4.59 x 10-3 mmol), eugenol (25.7 mg, 0.16

mmol) in acetone-d6 (about 1 mL). After acquisition of an initial spectrum to set the

integral values, 2.10 (1.0 mg, 1.65 x 10-3 mmol, 1 mol %) was transferred quantitatively

from a vial using acetone-d6 in several portions into the J. Young NMR tube. Total

reaction volume was adjusted to 1.0 mL by addition of acetone-d6.

Table 3.28. Isomerization of eugenol with 2.10

Time (min) Starting material Isomer

4 - 98.8

173

Isomerization with PS-1 and PSL-1 under neat conditions

Neat isomerization of 4-penten-2-ol with PS-1. Using a 2 dram vial with Teflon-lined

cap and 4-penten-2-ol (125.8 mg, 1.46 mmol) was mixed with few drops of 1,4-dioxane.



integral values. PS-1 (44.6 mg, 0.020 mmol, 2 mol %) was added and vial was sealed and

immersed in an oil bath at 70oC. The progress of the reaction was monitored by taking

the vial inside the glovebox and removing a sample by a Pasteur pipette tip from the

reaction mixture. Then the conical vial was returned to oil bath. Samples were analyzed

in acetone-d6 by 1H NMR, see Table 3.29.

Table 3.29. Neat isomerization of 4-penten-2-ol with PS-1

Time (h) Starting material (%) 2- and 3-alkenes (%) Product (%)

1 79.0 35.7 2.2

2 27.6 63.8 19.9

3 6.1 30.6 63.4

5 2.3 3.9 90.8

18 1.8 3.0 92.5

174

Neat isomerization of 4-penten-2-ol with PSL-1. The procedure described above was

carried out with 4-penten-2-ol (124.9 mg, 1.45 mmol), a few drops of 1,4-dioxane and

PSL-1 (46.6 mg, 0.020 mmol, 2 mol %).

Table 3.30. Neat isomerization of 4-penten-2-ol with PSL-1

Time (h) Starting material (%) 2- and 3-alkenes (%) Product (%)

1 8.8 13.3 77.5

2 4.8 1.0 90.7

Neat isomerization of eugenol with PS-1. Using a 2 dram vial with Teflon-lined cap,

eugenol (167.1 mg, 1.0 mmol) was mixed with 1,4-dioxane (21.0 mg, 0.24 mmol). A

small sample (<3 µL) was removed by capillary action into the tip of a Pasteur pipette


integral values. PS-1 (14.5 mg, 0.010 mmol, 1 mol %) was added and vial was sealed and

placed on a nutator. Progress of the reaction was monitored by stopping the nutator

briefly and removing a sample by a Pasteur pipette tip from the reaction mixture.

Samples are analyzed in acetone-d6 by 1H NMR and progress of isomerization specified

is tabulated.

Table 3.31. Neat isomerization of eugenol with PS-1


2 96.6 1.9

5 75.1 20.4

24 - >99.9

175

Neat isomerization of eugenol with PSL-1. The procedure described above was carried

out with eugenol (165.5 mg, 1.0 mmol), 1,4-dioxane (26.3 mg, 0.3 mmol), and PSL-1

(16.1 mg, 0.010 mmol, 1 mol %).

Table 3.32. Neat isomerization of eugenol with PSL-1


2 95.3 8.4

5 20.2 80.8

24 - >99.9

Neat isomerization of 2-allylcyclohexanone with PS-1. Using a 2 dram vial with

Teflon-lined cap, 2-allylcyclohexanone (140.4 mg, 1.0 mmol) was mixed with 1,4-

dioxane (12.6 mg, 0.14 mmol). A small sample (<3 µL) was removed by capillary action

into the tip of a Pasteur pipette and the sample was analyzed in acetone-d6 to get an initial

1H NMR spectrum to set the integral values. PS-1 (16.5 mg, 0.010 mmol, 1 mol %) was

added and vial was sealed and immersed in an oil bath at 70oC. Progress of the reaction

was monitored by taking the vial inside the glovebox and removing a sample by a Pasteur

pipette tip from the reaction mixture. Then conical vial is returned to oil bath. Samples

are analyzed in acetone-d6 by 1H NMR and progress of isomerization specified is

tabulated.

176

Table 3.33. Neat isomerization of 2-allylcyclohexanone with PS-1


1 13.8 82.3

2 9.3 86.0

5 9.1 90.3

24 6.7 70.4a

a Further isomerization to α, β unsaturated ketone, 2-propylidenecyclohexanone is observed. Neat isomerization of 2-allylcyclohexanone with PSL-1. The procedure described

above was carried out with 2-allylcyclohexanone (141.4 mg, 1.0 mmol) mixed with 1,4-

dioxane (12.4 mg, 0.14 mmol), and PS-1 (16.7 mg, 0.010 mmol, 1 mol %).

Table 3.34. Neat isomerization of 2-allylcyclohexanone with PSL-1


1 12.6 82.6

2 9.4 91.8

5 8.7 99.0

24 7.6 66.0a

a Further isomerization to α, β unsaturated ketone, 2-propylidenecyclohexanone is observed.

177

Sequential isomerization and metathesis reactions Silica-supported 2nd generation Grubbs-Hoveyda catalyst41 was prepared according to

literature in gram scale.

Figure 3.35. Sequential isomerization and metathesis of 4-allylanisole

Conversion of 4-allylanisole (run 1): In the glovebox, a J-Young NMR tube was

charged with PS-1 (8.9 mg, 6.0x10-3 mmol, 2 mol%) and acetone-d6 was added to swell

the polymer supported catalyst. In a separate vial, 4-allylanisole (45.3 mg, 0.31 mmol)

and tetrakis(trimethylsilyl)methane (1.0 mg, 3.28 x 10-3 mmol) were dissolved in

acetone-d6. A small sample (<3 µL) was removed by capillary action into the tip of a

Pasteur pipette and the sample was analyzed in acetone-d6 to get an initial 1H NMR

spectrum to set the integral values using tetrakis(trimethylsilyl)methane as internal

standard. The solution of substrate and internal standard was quantitatively transferred to

the J. Young NMR tube using portions of acetone-d6. The reaction was mixed by a

nutator at room temperature. Analysis of an aliquot by 1H NMR spectroscopy confirmed

completion of the reaction.

After complete isomerization to (E)-anethole, in the glovebox, the reaction

solution was decanted through a Pasteur pipette containing a cotton and silica plug into a

178

pre-weighed scintillation vial. The J. Young NMR tube was washed with additional

acetone (1 mL x 3) and washings were run through the plug. The plug was washed with

acetone and hexanes (1 mL each). Solvents were reduced under vacuum (45.1 mg

recovered). Additional tetrakis(trimethylsilyl)methane (1.6 mg, 5.25 x 10-3 mmol) was

weighed in the scintillation vial as internal standard and all material dissolved in hexanes

(0.4 mL). A small sample (<3 µL) was removed by capillary action into the tip of a

Pasteur pipette and the sample was analyzed in acetone-d6 to get an initial 1H NMR

spectrum to set the integral values using tetrakis(trimethylsilyl)methane as internal

standard. Another scintillation vial was charged with silica-supported 2nd generation

Grubbs-Hoveyda catalyst6 (201.9 mg, 0.65 mol % Ru), hexanes (0.6 mL) and equipped

with magnetic stir bar. The solution of (E)-anethole with tetrakis(trimethylsilyl)methane

was quantitatively transferred with portions of hexanes to the scintillation vial, giving a

total reaction volume of 5 mL. The scintillation vial was sealed and immersed in oil bath

at 70 °C outside the glovebox overnight (14h). After the scintillation vial was cooled to

room temperature, 0.1 mL was removed from the reaction solution inside the glovebox.

After reducing the solvents under vacuum, acetone-d6 was added as NMR solvent. 1H

NMR analysis showed 91.0 % metathesis product along with observation of 9.0% (E)-

anethole.

Conversion of 4-allylanisole (run 2, isolated): A second experiment was performed in

the same way as the first, alkene isomerization conditions are kept the same but higher

catalytic loading and shorter time was used to achieve metathesis reaction. PS-1 (8.7 mg,

6.0 x 10-3 mmol, 2 mol%), 4-allylanisole (47.1 mg, 0.32 mmol), and


179

(E)-anethole was obtained (40.5 mg, 86.0 %), which was then treated with silica-

supported 2nd generation Grubbs-Hoveyda catalyst (1006.8 mg, 9.96 x 10-3 mmol, 3.1

mol% Ru). After 2 h at 70 °C, analysis of an aliquot by 1H NMR spectroscopy revealed

87.8 % metathesis (and 12.2 % starting material left).

The metathesis product was isolated as a white solid (24.1 mg, 73.5 % yield by

mass). 1H NMR (400 MHz, chloroform-d) δ 7.44 (d, J = 8.8, 4H), 6.94 (s, 2H), 6.90 (d, J

= 8.8, 4H), 3.84 (s, 6H). Data were similar to the reported 1H NMR spectrum of (E)-4,4’-

dimethoxystilbene.55-57

Figure 3.36. Sequential isomerization and metathesis of eugenol

Conversion of eugenol: In the glovebox, a J. Young NMR tube was charged with PS-1

(10.3 mg, 7.0x10-3 mmol, 2 mol%) and acetone-d6 was added to swell the polymer

supported catalyst. In a separate vial, eugenol (48.8 mg, 0.30 mmol) and

tetrakis(trimethylsilyl)methane (1.2 mg, 3.94 x 10-3 mmol) were dissolved in acetone-d6.



integral values using tetrakis(trimethylsilyl)methane as internal standard. The solution of

180

substrate and internal standard is quantitatively transferred to the J. Young NMR tube

using portions of acetone-d6. The reaction is mixed by a nutator at room temperature.

Analysis of an aliquot by 1H NMR spectroscopy confirmed completion of the reaction.

After complete isomerization to (E)-isoeugenol, in the glovebox, the reaction solution

was decanted through a Pasteur pipette containing a cotton and silica plug into a pre-

weighed scintillation vial. The J. Young NMR tube was washed with additional acetone

(3 x 1 mL) and washings were run through the plug. The plug was washed with acetone

and hexanes (1 mL each). Solvents were reduced under vacuum (51.6 mg recovered,

solvent present by 1H NMR analysis).

After addition of hexanes (0.4 mL), a small sample (<3 µL) was removed by

capillary action into the tip of a Pasteur pipette and the sample was analyzed in acetone-

d6 to get an initial 1H NMR spectrum to set the integral values using

tetrakis(trimethylsilyl)methane as internal standard. Another scintillation vial was

charged with silica-supported 2nd generation Grubbs-Hoveyda catalyst (298.4 mg, 2.95 x

10-3 mmol Ru, 1.0 mol % Ru), hexanes (0.6 mL) and equipped with magnetic stir bar.

The solution of (E)-isoeugenol with tetrakis(trimethylsilyl)methane was quantitatively

transferred with portions of hexanes to the scintillation vial. Total reaction volume is 5

mL. The scintillation vial was sealed and immersed in oil bath at 70 °C outside the

glovebox overnight. After the scintillation vial was cooled to room temperature, 0.1 mL

was removed from the reaction solution inside the glovebox. After reducing the solvents

under vacuum, acetone-d6 was added as NMR solvent. 1H NMR spectroscopic analysis

showed 95.9 % metathesis product along with observation of 4.1 % (E)-isoeugenol. 1H

NMR (500 MHz, benzene-d6) δ 7.03 (d, J = 7.5, 2H), 7.00 (dd, J = 8.0, 1.5, 2H), 6.94 (s,

181

2H), 6.83 (d, J = 2.0, 2H), 5.48 (s, 2H), 3.21 (s, 6H). Data were in accordance with those

previously reported.43,55-58 1H NMR (400 MHz, chloroform-d) 7.02 (d, J = 8.8, 4H), 7.19

(s, 2H), 7.07 (d, J = 8.8, 4H), 3.95 (s, 6H).

Isolation of the eugenol possibly resulted in oxidation of the OH moiety suggested

by color change of the silica from green to deep red-brown and observance of additional

olefinic peaks around 5.8 and 4.9 ppm along with several new aromatic peaks and OCH3

peaks in 1H NMR spectrum.

Figure 3.37. Sequential isomerization and metathesis of protected eugenol, (4-allyl-2-methylphenoxy)(tert-butyl)dimethylsilane

Conversion of protected eugenol, (4-allyl-2-methoxyphenoxy)(tert-

butyl)dimethylsilane: In the glovebox, a J. Young NMR tube is charged with PS-1 (6.4

mg, 4.4 x 10-3 mmol, 2.2 mol%) and acetone-d6 were added to swell the polymer

supported catalyst. In a separate J. Young tube (4-allyl-2-methoxyphenoxy)(tert-

butyl)dimethylsilane (56.3 mg, 0.20 mmol) and tetrakis(trimethylsilyl)methane (2.1 mg,

6.89 x 10-3 mmol) were dissolved in about 1.0 mL acetone-d6. This sample was analyzed

in acetone-d6 to get an initial 1H NMR spectrum to set the integral values using

tetrakis(trimethylsilyl)methane as internal standard. The solution of substrate and internal

182

standard was quantitatively transferred to the J. Young NMR tube using portions of

acetone-d6. The reaction was mixed by a nutator at room temperature. Analysis of an

aliquot by 1H NMR spectroscopy confirmed completion of the reaction.

After complete isomerization to protected (E)-isoeugenol, in the glovebox, the

reaction solution was decanted through a Pasteur pipette containing a cotton and silica

plug into a pre-weighed scintillation vial. The J. Young NMR tube was washed with

additional acetone (3 x 1 mL) and washings were run through the plug. The plug was

washed with acetone and hexanes (1 mL each). Solvents were reduced under vacuum

(54.3 mg, 96.5% yield recovered).

After addition of hexanes (0.4 mL), a small sample (<3 µL) was removed by


d6 to get an initial 1H NMR spectrum to set the integral values using

tetrakis(trimethylsilyl)methane as internal standard. Another scintillation vial was

charged with silica-supported 2nd generation Grubbs-Hoveyda catalyst (968.3 mg, 9.6 x

10-3 mmol Ru, 4.8 mol % Ru), hexanes (3 mL) and equipped with magnetic stir bar. The

solution of protected (E)-isoeugenol with tetrakis(trimethylsilyl)methane was

quantitatively transferred with portions of hexanes to the scintillation vial, giving a total

reaction volume is 10 mL. The scintillation vial was sealed and immersed in oil bath at

60 °C outside the glovebox overnight. After the scintillation vial was cooled to room

temperature, the reaction solution was decanted through a Pasteur pipette containing a

cotton and silica plug into a pre-weighed vial. The reaction vial and silica-supported 2nd

generation Grubbs-Hoveyda catalyst were washed with warm toluene (3 x 5 mL) and

washings were run through the plug. Solvents were reduced under vacuum to give final

183

product as yellow liquid. (43.6 mg, 87.0 % yield).

1H NMR (500 MHz, chloroform-d) δ 7.01 (d, J = 2.0, 2H), 6.96 (dd, J = 2.0, 8.0, 2H),

6.91 (s, 2H), 6.83 (d, J = 8.0, 2H), 3.87 (s, 6H), 1.01 (s, 18H).

Data were similar to the reported 1H NMR spectrum of (E)-4,4’-dihydroxy-3,3’-

dimethoxystilbene. 43,55-58

Catalyst recycling and ruthenium leaching experiments performed with eugenol

The experiment is designed on the basis that Ru concentration is reliably detected

in the range of 1-10 ppm after the ICP-OES is calibrated with Ru standards (10, 1, and

0.1 ppm Ru) prepared from RuCl3.xH2O (42.43% Ru) with aqueous 2% HCl solution.

ICP-OES measurements were obtained on Perkin Elmer DV-4300 ICP-OES with

Meinhardt C nebulizer with a cyclonic spray chamber. The method used was power 1500

W, axial view, plasma flow 15 L/min, auxiliary flow 0.2 min/L, nebulizer flow 0.8 L/min

and sample flow 1.50 mL/min. Readings were taken at 240.272, 349.894 and 279.535

nm.

The ruthenium content of the combined filtrates and washes (5) was determined

by inductively coupled plasma optical emission spectroscopy (ICP-OES) analysis.

184

Table 3.35. Amount of starting material and internal standard used for recycling experiments

In the glovebox, immobilized catalyst (PS-1 11.1 mg, PSL-1 11.5 mg, 7.5x10-3

mmol, 1 mol%) was weighed in a conical vial and acetone was added to swell the

polymer-supported catalyst. In separate vials, eugenol and 1,4-dioxane (Table 3.35) was

added as internal standard. Acetone (0.5 mL) was added to ensure complete dissolution

of all material. A small sample (<3 µL) was removed by capillary action into the tip of a

Pasteur pipette and the sample was analyzed in acetone-d6 to get initial 1H NMR spectra

to set the integral values. The solution of substrate and internal standard for cycle I was

added to the conical vial. The substrate vial was washed with additional acetone and

washings were added to conical vial. The reaction volume was adjusted to 5 mL. The

reaction was mixed by a nutator at room temperature. After the isomerization reaction (1

h for PS-1, 1.5 h for PSL-1) the solution was moved from the conical vial to a

scintillation vial. A sample (0.1 mL) was placed in an NMR tube and acetone-d6 was

added as NMR solvent, and the resulting sample was analyzed by 1H NMR spectroscopy

to give the values in Table 3.36. PS-1 was washed in the conical vial with additional

PS-1 PSL-1

Cycle # Eugenol (mg) 1,4-Dioxane (mg) Eugenol (mg) 1,4-Dioxane (mg)

I 123.3 19.1 123.4 29.5

II 123.2 20.5 123.5 27.1

III 123.2 22.1 123.3 28.2

IV 123.4 23.4 123.2 26.2

V 123.3 22.8 123.4 26.2

185

acetone and the washings were added to the scintillation vial for the same cycle. The

residual PS-1 was dried in a conical vial under reduced pressure with oil-pump vacuum

for about 45 min. The solution of substrate and internal standard for cycle II was added to

the conical vial and the consecutive cycles were performed as just described.

The ruthenium leaching into the organic phase was determined by ICP. Acetone

solutions from the scintillation vials were reduced under vacuum to a volume of

approximately 0.2 mL and transferred to thick-walled and flame cut glass tubes. The

solutions were further concentrated under oil-pump vacuum to dryness. To the residue

was added 20 drops of concentrated HCl while cooling in an ice-water bath. Each tube

was placed under vacuum in liquid nitrogen and after the contents were frozen, the tube

was flame-sealed. After reaching room temperature, the flame-sealed tubes were

immersed in an oil bath at 80 °C overnight. After cooling to room temperature, the glass

tubes were scored with a glasscutter and snapped in two, and the contents were filtered

through a cotton plug into a 5 mL volumetric flask. The glass tubes were washed with DI

H2O in portions and the washings are added to the respective volumetric flasks. Aqueous

samples from each cycle were analyzed by ICP-OES.

Table 3.36. Isomerization activity from recycling experiments with PS-1 and PSL-1

PS-1 PSL-1 Cycle # % Eugenol % E-Isoeugenola % Eugenol % E-Isoeugenola

I 0.6 98.1 6.1 97.5

II 0.9 99.4 2.1 95.8

III 0.3 99.9 4.6 97.7

IV 0.2 98.4 2.9 97.8

V 0.2 97.1 9.5 94.9 a Percent yield calculated from 1H NMR

186

Results of these analyses show that 1.04 % of the initial 1% rutheunium loading

was lost after 5 cycles without any significant reduction in activity when PS-1 is used as

the catalyst. In other words, because 11.1 mg PS-1 contains 7.57 x 10-3 mmol Ru, and

7.86 x 10-5 mmol Ru was leached to the organic phase, therefore 1.04 % Ru was lost over

5 cycles. Extrapolating these results, if 1 g eugenol were used for isomerization, in the

first cycle, 43.8 µg Ru would be present in 1 g (E)-isoeugenol.

Table 3.37. Ruthenium leaching from recycling experiments performed with PS-1 and PSL-1

PS-1 PSL-1 Cycle # [Ru] (ppm) b [Ru] (ppm) b

I 1.08 0.41 II 0.51 0.33 III 0.17 0.06 IV 0.11 0.12 V 0.07 0.61

b Ru concentration from ICP-OES

Table 3.38. Leaching in mass ruthenium per cycle with PS-1

PS-1

Cycle # Eugenol (mg) [Ru] (ppm) Ru in 5 mL sample Ru in 5 mL sample

I 123.3 1.08 5.40 µg 5.34 x 10-5 mmol

II 123.2 0.51 2.55 µg 2.52 x 10-5 mmol

III 123.2 0.17 0.85 µg 8.41 x 10-6 mmol

IV 123.4 0.11 0.55 µg 5.44 x 10-6 mmol

V 123.3 0.07 0.34 µg 3.36 x 10-6 mmol

Total 616.4 9.69 µg 7.86 x 10-5 mmol • ppm = mg/L

187

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(50) Shin, J.; Jensen, S. M.; Ju, J.; Lee, S.; Xue, Z.; Noh, S. K.; Bae, C. Macromolecules 2007, 40, 8600. (51) Shin, J.; Bertoia, J.; Czerwinski, K. R.; Bae, C. Green Chem 2009, 11, 1576. (52) Desrochers, P. J.; Duong, D. S.; Marshall, A. S.; Lelievre, S. A.; Hong, B.; Brown, J. R.; Tarkka, R. M.; Manion, J. M.; Holman, G.; Merkert, J. W.; Vicic, D. A. Inorg Chem 2007, 46, 9221. (53) Pinchuk, A. N.; Rampy, M. A.; Longino, M. A.; Skinner, R. W. S.; Gross, M. D.; Weichert, J. P.; Counsell, R. E. J Med Chem 2006, 49, 2155. (54) De Feyter, S.; Abdel-Mottaleb, M. M. S.; Schuurmans, N.; Verkuijl, B. J. V.; van Esch, J. H.; Feringa, B. L.; De Schryver, F. C. Chem-Eur J 2004, 10, 1124. (55) Mali, R. S.; Jagtap, P. G. Synthetic Commun 1991, 21, 841. (56) Andrus, M. B.; Mendenhall, K. G.; Meredith, E. L.; Sekhar, B. B. V. S. Tetrahedron Lett 2002, 43, 1789. (57) Andrus, M. B.; Song, C.; Zhang, J. Q. Org Lett 2002, 4, 2079. (58) Warner, P.; Sutherland, R. J Org Chem 1992, 57, 6294.

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CHAPTER 4

MILD AND SELECTIVE HYDROGEN /

DEUTERIUM EXCHANGE AT ALLYLIC

POSITIONS OF OLEFINS

192

INTRODUCTION

Deuterium- and tritium-labeled compounds are widely used as research tools in

studies of drug metabolism, reaction mechanisms and kinetics, and structural elucidation

of biological macromolecules, among other purposes.1 The heavy isotopes of hydrogen

can be introduced either using multistep syntheses or by catalyzed exchange. The former

strategy involves several synthetic operations with labeled material. In contrast, catalyzed

exchange of hydrogen for deuterium or tritium is very attractive because it can be done in

one step, with existing unlabeled material, therefore, selective C-H bond activation by

metal complexes under mild conditions is a major area of research.2,3 Most of the

methods investigated require drastic conditions like high temperature and/or high

pressure (in conditions where D2 is the source of deuterium), acidic or basic additives.

The great challenge for catalyzed exchange is regio- and chemoselectivity and

functional group tolerance. Methods that label regioselectively with high efficiency using

either deuterium or tritium oxide are especially attractive because of the low cost and

toxicity of the labeling reagent.3 The H/D exchange of aromatic and aliphatic C-H bonds

have been investigated with various methods including acid, base and metal catalysis.

Garnett and co-workers reported one of the first examples in this area and demonstrated

exchange of aromatic hydrogens with deuterium using K2PtCl4 in presence of deuterium

oxide and acetic acid and deuteriochloric acid.4 Since then, regioselective and efficient

incorporation of deuterium into C-H bonds has become an important tool for preparation

of deuterium-labeled organic molecules. General procedures for the incorporation of

deuterium into the C-H bonds are often limited to aromatic and aliphatic C-H bonds of

193

organic compounds. Cp*Ir complexes with phosphine ligands5-9 or N-heterocyclic

carbene ligands10-12 have been shown to catalyze H/D exchange. These complexes can

use methanol-d4,10 deuterium oxide,5,8 or a methanol-d/deuterium oxide system12 as the

deuterium source. Among Cp*Ir-based catalysts, Cp*Ir(PMe3)Cl2, 4.1 reported by

Bergman5 et al. reaches high to moderate deuterium incorporation (Figure 4.1).

Figure 4.1. H/D exchange of aromatic and aliphatic C-H bonds reported by Bergman and coworkers

In 2003, Lin and Lau et al. reported H/D exchange between methane and

deuterated solvents such as benzene-d6, tetrahydrofuran-d8, diethylether-d10, 1,4-dioxane-

d8 using the ruthenium complex TpRu(PPh3)(CH3CN)H (Tp =

hydro(trispyrazolyl)borate).13 Later in 2007, they reported catalytic H/D exchange

between organic molecules and deuterium oxide at a reaction temperature of 110 oC.

Argon pressure (10 atm) was applied to ensure that reactants and reagents did not boil. At

0.4 mol% loading, TpRu(PPh3)(CH3CN)H is capable of incorporating 24 and 13 percent

deuterium into diethyl ether and tetrahydrofuran, respectively.14

Although there are many reports of H/D exchange at aromatic and aliphatic C-H

194

bonds15-26 there are fewer such reports for alkenes and much less work has been carried

out on direct catalytic H/D exchange between olefins and deuterium oxide. The high

temperature-dilute acid method has been explored in the 1980s for the H/D exchange

between deuterium oxide and olefins,27,28 however; the method suffers from side

reactions of skeletal rearrangements, acid catalyzed hydration of the alkene, or

polymerization and oligomerization of olefins.

H/D exchange catalyzed by Pd/C of cyclooctene and cyclohexene with deuterium

oxide (Figure 4.2) has been reported by Anet et al. at tempreratures of >140 oC and by

Matsubara29 et al. under hydrothermal conditions (250 oC, 5 MPa).

Figure 4.2. Deuteration of cyclooctene under hydrothermal conditions by Matsubara and coworkers

Later in 2007, Matsubara et al. demonstrated that cyclic olefins such as

cyclohexene and cyclodecene (Figure 4.3) can undergo H/D exchange with deuterium

oxide under microwave irradiation in the presence of homogenous catalyst RuCl2(PPh3)3

(5 mol%, 140 oC, 0.34 MPa) and sodium dodecylsulfate (SDS) as an additive. SDS

partially hydrolyzes to give dodecanol, which provides hydride and stabilizes the

ruthenium species by micelle formation.30

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Figure 4.3. Deuteration of cyclohexene using microwave irradiation

Brookhart et al. illustrated catalytic H/D exchange reactions (Figure 4.4) in which

deuterium can be transferred from deuterated solvents (benzene-d6, toluene-d8,

chlorobenzene-d5, or acetone-d6), to the CH bonds of alkenes bound on complex 4.2 at 50

°C. Thermolysis at higher temperatures results in further H/D exchange and deuteration

of both the SiMe3 and C5Me5 groups. Heating 4.2 in benzene-d6 with cyclopentene

resulted in moderate (49%) deuteration of vinylic, allylic and homoallylic sites. Higher

degrees of deuteration are observed with aniline, Cp2Fe, and EtOAc.17

Figure 4.4. H/D exchange reported by Brookhart and coworkers

When [Cp*Ir(PMe3)H3]OTf, a hydride analogue of 4.1, also reported by Bergman

et al. is used, deuterium incorporation into olefinic sites can be achieved. Reactions with

cyclohexene at 75 oC resulted in 95%, 83%, and 88% deuterium in vinylic, allylic, and

homoallylic positions, respectively, and for analogous positions on cyclopentene results

were 95%, 96%, and 90%, respectively. When 1-hexene was subjected to same reaction

conditions internal alkene isomers were observed. Overall, 26% of the vinylic positions

196

of 1-hexene were deuterated as were 23% of internal methylene positions, although the

terminal methyl group was not deuterated.8

Morrill et al. observed that partial deuteration of octene, cyclohexene, and styrene

during labeling studies of alkene isomerization using RhCl3/BH3 in the presence of D2O.

In the case of styrene, where no isomerization is possible the fact that deuterium

incorporation took place suggests that alkene insertion is responsible for H/D exchange.31

Amidoiridium hydride complex [(dtbpp)Ir(H)(NH2)] 4.3 (Figure 4.5, dtbpp = 1,5-

bis(di-tert-butylphosphino)pentan-3-yl), reported by Zhou et al.32 activates vinylic C-H

bonds and performs H/D exchange reactions with control of carbon-carbon double bond

isomerization and tolerance to different functional groups. The functional group

selectivity and tolerance is demonstrated by subjecting natural products, such as

forskolin, altrenogest, (Figure 4.5) and tiamulin to 4.3 to H/D exchange in benzene-d6 at

room temperature. Complex 4.3 also catalyzed H/D exchange of substituted aromatic

and heteroaromatic compounds, even pyridine, which can deactivate catalytic activity of

several other iridium complexes, presumably through competitive binding at nitrogen.8,33

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Figure 4.5. Scope of H/D exchange with [(dtbpp)Ir(H)(NH2)]

Although the study of H/D exchange reactions has tended to concentrate on

aromatic or aliphatic compounds, there is an increasing interest in the deuteration of

vinylic derivatives. Since 2009, several reports of H/D exchange have emerged. Li and

Jia, et al. investigated H/D exchange reactions using six-coordinate 18-electron

complexes MHCl(CO)(PPh3)3 (M = Ru, Os) and found that the readily available hydride

complex RuHCl(CO)(PPh3)3 can effectively catalyze H/D exchange reactions of

deuterium oxide with both terminal and internal alkenes. Through H/D exchange between

metal hydride and deuterium oxide, and reversible olefin insertion into a Ru-D(H) bond,

protons attached to alkene carbons and the alkyl chains of alkenes can all undergo H/D

exchange with deuterium oxide. Both terminal and internal alkenes, for example,

styrene, stilbene and cyclooctene can be deuterated.34

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Moreover, selectivity towards olefinic versus aromatic protons is an important

challenge. For example, Milstein’s pincer-type ruthenium hydride complex20,24 [Ru-(2,6-

bis((di-tert-butylphosphino)methyl)pyridine)(η2-H2)H2] can incorporate deuterium into

aromatic positions as well as olefinic positions. Oro et al. reported highly active and

selective H/D exchange at the β position of aromatic α-olefins by a rhodium(III)–N-

heterocyclic carbene–hydride catalyst that contains a bulky carbene, 3-bis-(2,6-

diisopropylphenyl)imidazol-2-carbene (IPr), and a chelating quinolinate ligand.

[RhClH(κ2O,N-(C9H6NO)(IPr)] exchanges β-H of olefinic sites and α-H exhange can be

controlled by the bulky IPr groups on the carbene.35

The overall challenge for catalyzed H/D exchange is regio-selectivity, and

chemoselectivity in presence of different functional groups. The review of literature

shows that research in H/D exchange has been heavily concentrated on aromatic,

aliphatic and vinylic sites of olefinic sites and many of the systems execute H/D

exchange of more than one type of C-H bond.

USE OF ALKENE ISOMERIZATION CATALYST 2.10 IN H/D EXCHANGE

In 2009, we reported H/D exchange at allylic positions of alkenes catalyzed by

recently reported alkene zipper catalyst 2.10 (see chapter 2) in homogeneous and biphasic

reactions using inexpensive deuterium oxide as the isotope source.36,37 Study of the

complex 2.10 has revealed that it is a versatile bifunctional catalyst suitable for the study

of catalytic isomerization of alkenes and H/D exchange of accessible allylic alkene

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protons. Bifunctional catalyst 2.10 has been reported to isomerize various other

functionalized olefins including, but not limited to, alkenols, silyl ethers, amines, and

esters. As mentioned in chapter 3, distinguishing characteristics of 2.10 include formation

of (E)-isomer products with low catalyst loadings (2-5 mol%) at moderate temperatures

(25-70°C).38

The imidazole group on the phosphine ligand is proposed to act as an internal

base facilitating the isomerization by deprotonating accessible allylic position(s) of a

coordinated alkene. The protonated nitrogen could be expected to undergo H/D exchange

in the presence of deuterium oxide. In order to investigate the mechanism proposed in

Figure 5.6 and explore possible application of 2.10, deuterium oxide was added to the

isomerization reactions.

In our experiments, substrate was dissolved in acetone-d6 and deuterium oxide

was added to provide 20 D for each exchangeable H present in the substrate. For

example, 1-butene has eight exchangeable protons, therefore, 80 equivalents of deuterium

oxide was added to the reaction. Assuming equal distribution of D among all

exchangeable positions, each such position should be 95% deuterated, judged to be a

synthetically useful goal. The effects of isotope fractionation have also been considered.

Experimental data summarized in Table 9 of reference 39 for ethylene and methane

suggests that insignificant fractionation between vinylic and alkyl C-H bonds should

occur, and the effect of fractionation between these hydrocarbon C-H bonds and the O-H

bonds should have less than 1-2% effect on the degree of substrate deuteration under our

conditions.39

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Progress of the reaction was monitored by 1H NMR spectroscopy; deuteration is

calculated from integration and corrections are done according to theoretical deuteration.

For a reaction at elevated temperatures, the reaction was set up in the same manner

described above and the J. Young NMR tube was immersed in an oil bath at 70 °C.

When 1-propene is exposed to 2.10 and deuterium oxide, deuterium incorporation

is observed only at C1 and C3, reaching 97.5-98.5% of theoretical deuteration within 24

h (Figure 4.7). In stark contrast, the single proton at C2 remained intact (as observed up

to 60 d). Similar deuteration at only C1 and C3 was seen when 4-allylanisole was heated

with 2.10 and deuterium oxide at 70 °C. Isomerization of diallyl ether gave (E, E)-

dipropenyl ether without any detectable (E, Z)- or (Z, Z)-isomer.7 In presence of

deuterium oxide, H/D exchange is seen only at positions C1 and C3,7 consistent with the

other two examples.

The observed selectivity, retention of H at C2, renders the alternative mechanism,

metal hydride formation, alkene insertion, and β-hydride elimination, seen for many other

alkene isomerization catalysts40-43 highly unlikely (Chapter 2).

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Figure 4.6. Proposed mechanism of isomerization and deuteration by 2.10

The case of 4-allylanisole deserves additional comment. Isomerization of the

double bond is complete within 5 min at room temperature, yet full deuteration requires

days at 70 oC. This is consistent with the high selectivity, dictated by sterics, of 2.10

(Figure 4.6; see also Figures 2.10 and 2.11 in Chapter 2 and discussion).

In contrast to the case of substrates with isolated allyl groups, where the alkene

can migrate over two bonds or more, (E)-2-butene and 1-pentene were exposed to

deuterium oxide and 2.10; H/D exchange occurred at previously unreactive vinylic

positions and total deuteration was observed (Figure 4.7). Presumably η3-allyl

intermediates (Figure 4.6) formed along the chain, allowing all positions to become

allylic through isomerization. Thus, full deuteration of these substrates can be achieved

with 2 to 5 mol % catalyst loading and reasonable reaction times.

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Figure 4.7. Isomerization of linear olefins

The very high kinetic selectivity of the catalyst for making or acting on (E)-

alkenes without isomerization to (Z)-alkenes is highlighted by the following experiments

with isomers of butene with either D2O or H2O as a control. Starting with either (E)- or

(Z)-2-butene and 2 mol % 2.10, the half-life for equilibration of the two isomers was

measured to be about 10 days, a result unchanged by addition of H2O (Figure 4.8). In

comparison, exposure of (E)-2-butene to 2.10 and deuterium oxide led to complete

deuteration within 24 h, without formation of detectable formation of the (Z)-isomer.

Thus, 2.10 deuterates (E)-2-butene quickly (t1/2 = ca. 1.2 h), but only slowly (t1/2 > ca.

240 h) isomerizes it to the (Z)-isomer, a rate difference of ca. 200-fold! Exposure of (Z)-

2-butene to 2.10 and deuterium oxide showed lack of deuterium incorporation to (Z)-2-

butene unless it isomerized to (E)-2-butene. These experiments shed valuable

203

mechanistic insight on the action of 2.10. The isomerization of (E)-alkenes to terminal

alkenes is shown by perdeuteration of 1-pentene (vide supra).

Figure 4.8. (left) 1H NMR spectrum of 2-butene in presence of water. Geometrical isomerization to a mixture of (E)- (major) and (Z)- (minor) 2-butenes in acetone-d6; (right) 1H NMR spectrum of 2-butene in presence of deuterium oxide. Conclusion: Deuteration is much more rapid than geometrical isomerization.

Branched substrates (Figure 4.9) provide additional examples of highly selective

deuteration. For example, 4-methyl-1-pentene isomerized to (E)-4-methyl-2-pentene and

deuteration was observed only at C1 and C3, leaving the C2 proton intact.9 Further

isomerization was not observed even at elevated temperatures over time. Selective

deuteration is observed with branched substrates. The natural product (+)-limonene

underwent H/D exchange mainly at the exocyclic isopropenyl group. Deuterium

incorporation is observed at the endocyclic double bond but is far from complete, which

can be attributed to steric hindrance to 1 forming an η3-allyl complex at this position.

Deuteration of (+)-valencene was even more selective. Exocyclic isopropenyl groups are

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found in many terpenoid natural products, hence facile pentadeuteration at such sites is of

particular interest.

Figure 4.9. Isomerization and selective deuteration of branched olefins

Biphasic reactions were performed on liquid substrate 4-allylanisole by stirring it

with only catalyst and deuterium oxide. Higher deuterium content was reached in shorter

time compared to homogeneous reactions (Figure 4.10). In a biphasic experiment setting

where deuterium oxide was added in portions, phase separation allows for extraction of

the aqueous phase. Removal of the aqueous phase after equilibration to ca. 80%

deuteration and recharging the reaction system with fresh deuterium oxide allows for

further exchange. Loss of catalyst during extraction is negligible since the catalyst 2.10 is

dissolved in the organic phase and coloration of aqueous phase is minimal. Remarkably,

in these experiments there was no need to add surfactants or other ionic materials to

achieve the proper distribution of catalyst between the two phases.

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Figure 4.10. Comparison progression of isomerization and H/D exchange of 4-allylanisole in homogeneous and biphasic settings over time

Attempts to exchange hydrogens for deuterium failed with cyclohexene and

cyclooctene. In cases with primary or secondary alcohols like 4-penten-1-ol or 4-penten-

2-ol, although deuterium incorporation was achieved, high isotope content was not

achieved possibly due to aldehyde or ketone formation providing a stable product

rendering the reaction irreversible.

In conclusion, unlike previous catalysts, 2.10 exchanges allylic protons of olefins

with deuterium from deuterium oxide with outstanding control of isomerization when it

occurs. Deuterium oxide is an attractive isotope source because of its low cost, safety,

and low toxicity and ease of handling. An exceptional degree of deuteration is achieved

206

at positions accessible by isomerization in homogeneous and biphasic reaction settings.

The high steric selectivity of 2.10 for (E)-alkenes gives the catalyst a distinctive reactivity

and selectivity profile, which is especially useful in labeling complex substrates either at

a late stage of a synthesis, or using material directly from natural sources, as illustrated

by the cases of (+)-limonene and (+)-valencene.

207


All manipulations were carried out in a nitrogen filled glovebox or using Schlenk

techniques. D2O, acetone-d6 and THF-d8 were received from Cambridge Isotope

Laboratories, Inc., and further deoxygenated by bubbling N2 gas through the liquid prior

to use. D2O had a deuterium content of 99.9% and was stored and used in the glovebox to

avoid dilution with atmospheric moisture. NMR spectra were obtained at 30 °C on either

a 500-MHz INOVA (500 MHz listed below for 1H = 499.940 MHz and 125.7 MHz for

13C = 125.718 MHz), a 400-MHz Varian NMR-S (400 MHz listed below for 1H =

399.763 MHz and 100 MHz for 13C = 100.525 MHz), or a 200 MHz Gemini (31P data at

80.95 MHz) spectrometer. 1H NMR chemical shifts were reported as mentioned in

chapter 2.

Calculation of Deuterium Content

Degree of deuteration can be expressed in a wide variety of ways. In this work, our major

goal was to perform experiments with sufficient deuterium source that a synthetically

appealing and useful degree of deuteration (greater or equal to 95%) could be obtained.

Here in this section using one example (for Table 4.3) we calculate observed deuteration

as a per cent of the theoretical maximum, taking into account not only the ratio of

available deuterium (from deuterium oxide, D2O), to the number of exchangeable H on

the substrate (for example 4-allylanisole has 5 exchangeable protons), but also taking into

account the measured amount of protium in the D2O used (called HDO below). The D2O

208

employed in this work had a nominal deuterium content of 99.9%, and was stored and

used in the glovebox to avoid any dilution by atmospheric water.

Amount of 4-allylanisole weighed 29.9 mg

Total number of moles of hydrogen in 4-allylanisole (including non-exchangeable ones)

From 1H-NMR Spectrum

Integration of HDO peak is 8.81 units, giving

Now to calculate the total mmol of exchangeable H (from both HDO and substrate) and

D (from the D2O and its HDO impurity):

209

Theoretically maximum deuteration (assumed for simplicity to be same at all

exchangeable positions) is:

93.9 x (100 ÷ 94.8) = 99.1 % of the theoretical maximum deuteration.

Figure 4.11. Deuteration of propene

Deuteration of propene. Propene was bubbled through a J. Young NMR tube containing

1,4-dioxane (1.6 mg, 0.018 mmol) in acetone-d6 (about 1 mL). After determination of the

number of moles of propene (0.21 mmol) present, deuterium oxide (206.8 g, 10.3 mmol)

was added to the tube followed by 2.10 (2.5 mg, 0.0042 mmol, 2 mol %), transferred

quantitatively from a vial using acetone-d6 in several portions. Total reaction volume was

adjusted to 2.0 mL by addition of acetone-d6. Hydrogen-deuterium exchange was

observed via 1H NMR at several time intervals (Table 4.1). Starting material 1H NMR

(500 MHz, acetone-d6) δ 5.76 (qdd, J = 6.4, 10.2, 16.8 Hz, 1H), 4.95 (qdd, J = 1.8, 2.2,

16.8 Hz, 1H), 4.85 (qdd, J = 1.6, 2.4, 10.1 Hz, 1H), 1.62 (ddd, J = 1.4, 1.8, 6.4 Hz, 3H).

Product 1H NMR at 24 h (500 MHz, acetone-d6) δ 5.76 (bs, 1H), 4.96 (d, J = 17 Hz,

0.085H), 4.86 (d, J = 10 Hz, 0.085H), 1.64-1.59 (m, 0.20H).

Table 4.1. % Hydrogen left at indicated positions of propene after specified time

Time (min) 1 2 3

0 106.7 93.8 101.6

1 50.9 109.2 38.9

2 24.9 101.2 17.9

5 9.8 99.3 7.9

24 7.5 96.7 6.5

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Note on 2-butene NMR spectra. Both 2-butene isomers are examples of A3A’3XX’

proton spin systems, and their 1H NMR spectra (Fig. 4.12) are non-first-order. Here we

report methyl and methine proton signals as “m,” meaning A3A’3 of A3A’3XX’ for

methyl protons and XX’ of A3A’3XX’ for methine protons. In the literature44,45 these

peaks are reported variously as either d or dd when in fact they are not first order.

Rummens and Kaslander reported observed coupling constants for (Z)- and (E)-2-butene

in Canadian Journal of Spectroscopy, 1972, 17, 99-102.46

Figure 4.12. 1H NMR Spectrum of (E)-2-butene in acetone-d6 (upper); (E)- (major) and (Z)- (minor) 2-butenes in acetone-d6

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Figure 4.13. Control experiment with (Z)-2-butene in presence of water

Isomerization of (Z)-2-butene in presence of H2O. (Z)-2-butene was bubbled through a

J. Young NMR tube containing 1,4-dioxane (4.3 mg, 0.049 mmol) and acetone-d6 (about

1 mL). After determination of the number of moles of (Z)-2-butene (0.158 mmol) present,

water (28.5 g, 1.58 mmol, 10 equiv) was added followed by 2.10 (1.9 mg, 0.0032 mmol,

2 mol %), transferred quantitatively from a vial using acetone-d6 in several portions into

the J. Young tube. Total reaction volume was adjusted to 2.0 mL by addition of acetone-

d6. Reaction observed via 1H NMR in several time intervals (Table 5.2). Starting

material 1H NMR (500 MHz, acetone-d6) δ 5.44-5.37 (m, 2H), 1.59-1.52 (m, 6H). 1H

NMR at 840 h (500 MHz, acetone-d6) δ 5.464-5.35 (m, 2H), 1.58-1.57 (m, 3.03H), 1.56-

1.55 (m, 2.86H).

Table 4.2. % Hydrogen atoms present at specified positions in reaction of (Z)-2-butene in presence of water

Time (min) 1 2 2’ (Z):(E) ratioa

0 1.99 6.01 - 1:0

5 2.01 6.07 - 1:0

48 1.99 5.42 0.60 1:0.1

240 2.02 4.43 1.58 1:0.4

480 1.98 3.79 2.28 1:0.6

840 1.93 2.86 3.03 1:1.1 a Ratio of (Z)- and (E)-isomers are calculated from integration of assigned methylene

peaks.

212

In a control experiment to show that catalyst was still active, 50 d after addition of 2.10,

1-pentene (2.1 mg, 0.030 mmol) was added to the J. Young NMR tube. In 1 h, 51.9% 1-

pentene had isomerized to 2-pentene, and in 22 h 1-pentene was completely isomerized.

Note on geometrical isomerization of 2-butenes: Isomerization of (Z)-2-butene to (E)-

2-butene has been observed previously47,48 as well. Considering the equilibrium constants

reported in these reports, (Z)-(E) isomerization has not yet reached equilibrium in our

experiments.

Note: Isotope exchange between the solvent (acetone-d6) and H2O can take place over

prolonged periods. If this is the case, (E)-2-butene will undergo hydrogen-deuterium

exchange and in turn, (E)-2-butene-d8 can undergo geometric isomerization to give (Z)-2-

butene-d8. The NMR measurements used cannot determine the amount (Z)-2-butene-d8

that may be present in the reaction mixture.

Figure 4.14. Control experiment with (Z)-2-butene in presence of deuterium oxide

Isomerization of (Z)-2-butene in presence of deuterium oxide. (Z)-2-butene was

bubbled through a J. Young NMR tube containing 1,4-dioxane (3.6 mg, 0.041 mmol) and

acetone-d6 (about 1 mL). After determination of the number of moles of (Z)-2-butene

(0.199 mmol) present, deuterium oxide (311.6 mg, 15.6 mmol, 78.2 equiv) was added

followed by 2.10 (2.4 mg, 0.0040 mmol, 2 mol %), transferred quantitatively from a vial

using acetone-d6 in several portions into the J. Young tube. The vial containing 2.10 was

213

washed with additional acetone-d6 and washings were added to the tube. Total reaction

volume was adjusted to 2.0 mL by addition of acetone-d6. Reaction was observed via 1H

NMR at several time intervals (Table 4.3). Starting material 1H NMR (500 MHz,

acetone-d6) δ 5.44-5.37 (m, 2H), 1.50-1.47 (m, 6H). 1H NMR at 840 h (500 MHz,

acetone-d6) δ 5.44-5.34 (m, 0.54H), 1.52-1.49 (m, 1.59H); 2D NMR at 822 h (400 MHz,

acetone-d6) δ 5.36, 1.47.

Table 4.3. % Hydrogen atoms present at specified positions in reaction of (Z)-2-butene in presence of deuterium oxide

Time (min) 1 2

0 100.5 100.5

5 98.5 100.5

48 94.0 96.3

240 69.0 68.2

480 45.5 46.2

840 27.0 26.5


1-pentene (2.3 mg, 0.033 mmol) was added to the J. Young NMR tube. In 1 h, 68.3% 1-

pentene had isomerized to 2-pentene, and in 22 h 1-pentene was completely isomerized.

Note: Apparent reduction of the amount of (Z)-2-butene is due to its geometrical

isomerization into (E)-2-butene (vide supra), which undergoes hydrogen-deuterium

exchange in presence of deuterium oxide.

214

Figure 4.15. Control experiment with (E)-2-butene in presence of water

Isomerization of (E)-2-butene in presence of H2O. (E)-2-butene (2.0 mL, 0.082 mmol)

was bubbled through a J. Young tube containing 1,4-dioxane (10.8 mg, 0.123 mmol) and

H2O (7.8 mg, 0.43 mmol) in acetone-d6 (about 0.8 mL). After acquisition of an initial

spectrum to set the integral values, 2.10 (1.1 mg, 0.0018 mmol, 2 mol %) was transferred

quantitatively from a vial using acetone-d6 in several portions to the J. Young NMR tube.

The vial containing 2.10 was washed with additional acetone-d6 and washings were added

to the tube. Reaction was observed via 1H NMR in several time intervals (Table 5.4).

Starting material (400 MHz, acetone-d6) δ 5.43-5.40 (m, 2H), 1.60-1.59 (m, 6H). 1H

NMR at 216 h (400 MHz, acetone-d6) δ 5.46-5.40 (m, 1.88H), 1.60-1.57 (m, 5.53H).

Table 4.4. % Hydrogen atoms present at specified positions in reaction of (E)-2-butene in presence of water

Time (min) 1 2 2’ (Z):(E) ratioa

0 103.5 98.8 - -

24 94.5 91.7 8.0 11.5:1

48 94.5 91.2 9.2 9.9:1

96 94.5 84.3 12.0 7.0:1

144 94.0 80.2 16.2 5.0:1

216 94.0 71.5 20.7 3.5:1 a Ratio of (Z)- and (E)-isomers are calculated from integration of assigned methylene peaks.

215

Figure 4.16. Deuteration of (E)-2-butene

Deuteration of (E)-2-butene. (E)-2-butene was bubbled through a J. Young NMR tube

containing 1,4-dioxane (3.7 mg, 0.042 mmol) in acetone-d6 (about 1 mL). After

determination of the number of moles of (E)-2-butene (0.19 mmol) present, deuterium

oxide (206.6 g, 15.3 mmol) was added followed by addition of 2.10 (2.4 mg, 0.0039

mmol, 2 mol %), transferred quantitatively from a vial using acetone-d6 in several

portions into the J. Young tube. Total reaction volume was adjusted to 2.0 mL by

addition of acetone-d6. Reaction was observed via 1H NMR at several time intervals

(Table 5.5). After 24 h, 2.10 was inactivated by briefly bubbling carbon monoxide gas

through the tube. Starting material 1H NMR (400 MHz, acetone-d6) δ 5.39-5.29 (m, 2H),

1.52-1.51 (m, 6H). Product at 24 h 1H NMR (400 MHz, acetone-d6) δ 5.38-5.42 (m,

0.09H), 1.52-1.48 (m, 0.10H). 2D NMR (61.366 MHz, acetone-d6) δ 5.353, 1.514, 1.477.

13C NMR (150.823 MHz, acetone-d6) 126.18-125.71 (m), 17.44-16.64 (m).

Note: In the 13C NMR spectrum of an authentic (Z)- and (E)-2-butene mixture in acetone-

d6 peaks at 124.5, 124.2, 17.0, 11.4 ppm are observed. Peaks at 124.2 and 11.4 ppm are

assigned to the (Z) isomer and peaks at 124.5 and 17.0 ppm are assigned to the (E) isomer

according to literature. (Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. Spectrometric

Identification of Organic Compounds; 1981; p 263; Wang, R.; Groux, L. F.; Zargarian,

D. Organometallics 2002, 21, 5531-5537) Looking at the methyl region of the spectrum,

one will be able to observe presence of cis isomer clearly. In our experiment (Z) isomer

was not detected; the estimated detection limit is as high as 10%, because the 13C NMR

216

peaks for fully deuterated material are split by the D nuclei, hence achieving reasonable

signal-to-noise on the sample above required nearly 2 days).

Table 4.5. % Hydrogen atoms present at specified positions in reaction of (E)-2-butene in presence of deuterium oxide

Time (min) 1 2

0 97.9 100.7

1 56.6 59.7

5 18.7 13.1

24 4.6 5.0


1-pentene (7.2 mg, 0.10 mmol) was added to to the J. Young NMR tube. In 20 h, 1-

pentene had completely isomerized to 2-pentene.

Figure. 4.17. Isomerization and deuteration of 1-pentene

Isomerization and deuteration of 1-pentene. A J. Young NMR tube was charged with

tetrakis(trimethylsilyl)methane (a few small crystals), 1-pentene (7.1 mg, 0.10 mmol) and

deuterium oxide (201.3 mg, 10.0 mmol) in acetone-d6 (1.0 mL). After acquisition of an

initial spectrum to set the integral values, 2.10 (3.0 mg, 0.0049 mmol, 5 mol %) was

transferred quantitatively from a vial using acetone-d6 in several portions into the J.

Young NMR tube. Progress of the reaction was monitored via 1H NMR (refer to table

5.6). Starting material 1H NMR (500 MHz, acetone-d6) δ 5.75 (ddt, J = 6.5, 10.5, 15.5

Hz, 1H), 4.93 (ddt, J = 1.5, 2.0, 17.0 Hz, 1H), 4.87 (ddt, J = 1.5, 2.0, 10.0 Hz, 1H), 1.95

217

(~tdd, 4JH1-H3 = 2.0 Hz, 3JH2-H3 = 3JH3-H4 = 7.4 Hz, 2H), 1.33 (tq, 3JH4-H5 = 3JH3-H4 = 7.5

Hz, 2H), 0.83 (t, J = 7.2 Hz, 3H). Product 1H NMR at 24 h (500 MHz, acetone-d6) δ 5.38

(bs, 0.05H), 5.32 (bs, 0.06H), 1.85 (bs, 0.09H), 1.50 (bs, 0.16H), 0.85-0.81 (m, 0.26H).

Table 4.6. % Hydrogen atoms present in 2-pentene with deuterium oxide at room temperature

Time (min) % H in 2-pentene

1 57.4

2 36.8

24 6.2

Isomerization and deuteration of 1-pentene at 70 oC. A J. Young NMR tube was

charged with tetrakis(trimethylsilyl)methane (a few small crystals), 1-pentene (7.2 mg,

0.10 mmol) and deuterium oxide (200.1 mg, 10.0 mmol) in acetone-d6 (1.0 mL). After

acquisition of an initial spectrum to set the integral values, 2.10 (1.3 mg, 0.0021 mmol, 2

mol %) was transferred quantitatively from a vial using acetone-d6 in several portions into

the J. Young NMR tube. The J. Young NMR tube was placed in an oil bath at 70 oC.

Progress of the reaction was monitored via 1H NMR (Table 5.7). Starting material 1H

NMR (500 MHz, acetone-d6) 5.75 (ddt, J = 6.5, 10.5, 15.5 Hz, 1H), 4.93 (ddt, J = 1.5,

2.0, 17.0 Hz, 1H), 4.87 (ddt, J = 1.5, 2.0, 10.0 Hz, 1H), 1.95 (~tdd, 4JH1-H3 = 2.0 Hz, 3JH2-

H3 = 3JH3-H4 = 7.4 Hz, 2H), 1.33 (tq, 3JH4-H5 = 3JH3-H4 = 7.5 Hz, 2H), 0.83 (t, J = 7.2 Hz,

3H). Product 1H NMR at 24 h (500 MHz, acetone-d6) δ 5.38 (bs, 0.05H), 5.32 (bs,

0.08H), 1.86 (bs, 0.10H), 1.51 (bs, 0.20H), 0.86-0.79 (m, 0.28H).

218

Table 4.7. % Hydrogen atoms present in 2-pentene with deuterium oxide at 70 oC

Time (min) % H in 2-pentene

1 32.8

2 18.7

5 8.2

24 6.9

Figure 4.18. Isomerization and deuteration of 4-allylanisole

Isomerization and deuteration of 4-allyl anisole. A J. Young NMR tube was charged

with tetrakis(trimethylsilyl)methane (a few small crystals), 4-allyl anisole (29.8 mg, 0.20

mmol), deuterium oxide (160.3 mg, 8.0 mmol) in acetone-d6 (about 1 mL). After



the J. Young NMR tube. Total reaction volume was adjusted to 2.0 mL by addition of

acetone-d6. 4-allyl anisole isomerized and deuterated to trans-anethole-d4, as specified in

Table 4.8. The data in Table 4.9 are for a reaction at elevated temperatures, where the

reaction was set up in the same manner described above and the J. Young NMR tube was

immersed in an oil bath at 70 °C. Starting material 1H NMR (500 MHz, acetone-d6) δ

7.07 (~d, AA’ of AA’BB’, J = 8.8 Hz, 2H), 6.73 (~d, BB’ of AA’BB’, J = 8.8 Hz, 2H),

5.91 (tdd, J = 6.8, 10.0, 16.8 Hz, 1H), 5.01 (tdd, J = 1.6, 2.0, 17.2 Hz, 1H), 4.96 (tdd, J =

219

1.2, 2.0, 10.0 Hz, 1H), 3.73 (s, 3H), 3.27 (d, J = 6.8 Hz, 2H). Product 1H NMR after 144

h at RT (500 MHz, acetone-d6) δ 7.26 (~d, AA’ of AA’BB’, J = 9.2 Hz, 2H), 6.83 (~d,

BB’ of AA’BB’, J = 8.8 Hz, 2H), 6.34-6.30 (m, 0.39H), 6.13-6.05 (bs, 0.97H), 3.74 (s,

2.92H), 1.80-1.73 (m, 0.18H); 2D NMR at 144 h (400 MHz, acetone-d6) δ 6.37-6.33 (m),

1.75-1.73 (m). In the case of the RT reaction, 31P NMR taken at 65 d showed a peak for

2.10 along with peaks for three other species.

Table 4.8. % Hydrogen left at indicated positions of (E)-anethole after specified time at room temperature

Time (min) 1 2 3

1 90.7 100.1 50.7

2 85.1 98.2 41.3

5 80.7 98.7 28.0

24 67.4 99.8 8.8

48 58.5 98.7 6.4

144 39.2 97.0 6.0

Table 4.9. % Hydrogen left at indicated positions of (E)-anethole after specified time at 70 oC

Time (min) 1 2 3

1 74.7 99.5 40.3

2 64.3 97.2 27.7

5 47.7 97.2 14.5

24 21.4 96.7 7.2

48 14.0 95.8 6.7

144 12.7 97.7 6.1

220

Isomerization and deuteration of 4-allyl anisole in a biphasic reaction setting. A

conical vial was charged with tetrakis(trimethylsilyl)methane (a few small crystals), 4-

allyl anisole (148.6 mg, 1.00 mmol), deuterium oxide (1.0042 g, 50.1 mmol) is added to

the conical vial and charged with a magnetic stir bar. A small sample (<3 µL) was

removed by capillary action into the tip of a Pasteur pipette and the sample was analyzed

in acetone-d6 to get an initial spectrum to set the integral values. In the glovebox, 2.10

(12.2 mg, 0.020 mmol, 2 mol %) was transferred quantitatively from a vial using acetone-

d6 in several portions to the reaction mixture. Progress of the reaction was monitored by

stopping the stirring briefly to allow phase separation, and removing a sample by a

Pasteur pipette tip from the top organic layer. The observed degree of deuteration is

specified in Table 5.10. Starting material 1H NMR (500 MHz, acetone-d6) δ 7.10 (~d,

AA’ of AA’BB’, J = 8.8 Hz, 2H), 6.85 (~d, BB’ of AA’BB’, J = 8.8 Hz, 2H), 5.94 (tdd, J

= 6.8, 10.0, 16.8 Hz, 1H), 5.05 (tdd, J = 1.6, 2.0, 17.2 Hz, 1H), 5.00 (tdd, J = 1.2, 2.0,

10.0 Hz, 1H), 3.76 (s, 3H), 3.31 (d, J = 6.8 Hz, 2H). Product 1H NMR at 96 h (500 MHz,

acetone-d6) δ 7.29 (~d, AA’ of AA’BB’, J = 9.2 Hz, 2H), 6.85 (~d, BB’ of AA’BB’, J =

8.8 Hz, 2H), 6.37-6.34 (m, 0.02H), 6.10 (bs, 0.98H), 3.77 (s, 2.92H), 1.80-1.75 (m,

0.18H).

221

Table 4.10. % Hydrogen left at indicated positions of (E)-anethole after specified time at room temperature under biphasic setting

Time (min) 1 2 3

1 93.2 99.6 59.7

2 87.2 98.6 35.9

5 73.7 99.2 16.3

24 31.3 99.1 4.7

48 11.4 98.5 3.9

72 5.7 98.6 3.5

Demonstration of the ability to wash out H using two successive “extractions” with

D2O: Isomerization and deuteration of 4-allyl anisole in a biphasic reaction setting.

A conical vial was charged with tetrakis(trimethylsilyl)methane (3.2 mg), 4-allyl anisole

(297.1 mg, 2.00 mmol), deuterium oxide (402.9 mg, 20.1 mmol) is added to the conical

vial and charged with a magnetic stir bar. A small sample (<3 µL) was removed by


d6 to get an initial spectrum to set the integral values. In the glovebox, 2.10 (24.3 mg,

0.040 mmol, 2 mol %) was transferred to the reaction mixture. The sealed conical vial

was immersed in an oil bath at 70 oC. Progress of the reaction was monitored by stopping

the stirring briefly to allow phase separation, and removing a sample by a Pasteur pipette

tip from the top organic layer. At 24 h, when maximum theoretical deuteration is reached,

as much of the aqueous layer as possible (312.1 mg) was removed with a micro-syringe

and a fresh batch of deuterium oxide (418.1 mg, 20.9 mmol) was added. Further

deuteration was observed after 24 h of heating (total 48 h). The observed degree of

222

deuteration is specified in Table 4.11. Starting material 1H NMR (500 MHz, acetone-d6)

δ 7.10 (~d, AA’ of AA’BB’, J = 8.8 Hz, 2H), 6.85 (~d, BB’ of AA’BB’, J = 8.8 Hz, 2H),

5.94 (tdd, J = 6.8, 10.0, 16.8 Hz, 1H), 5.05 (tdd, J = 1.6, 2.0, 17.2 Hz, 1H), 5.00 (tdd, J =

1.2, 2.0, 10.0 Hz, 1H), 3.76 (s, 3H), 3.31 (d, J = 6.8 Hz, 2H). Product 1H NMR at 48 h

(500 MHz, acetone-d6) δ 7.29 (~d, AA’ of AA’BB’, J = 9.2 Hz, 2H), 6.85 (~d, BB’ of

AA’BB’, J = 8.8 Hz, 2H), 6.37-6.34 (m, 0.09H), 6.10 (bs, 0.96H), 3.77 (s, 3H), 1.80-1.75

(m, 0.16H).

Table 4.11. % Hydrogen left at indicated positions of (E)-anethole after specified time at 70 oC under biphasic setting

Time (min) 1 2 3

1 92.1 98.7 81.7

5 56.0 100.0 39.9

24 21.3 99.6 18.4

48a 9.9 96.1 5.3 a Twenty-four hours after removal of first portion of D2O and addition of the second,

fresh portion.

Figure 4.19. Isomerization and deuteration of allyl ether

Isomerization and deuteration of allyl ether. A J. Young NMR tube was charged with

tetrakis(trimethylsilyl)methane (a few small crystals), diallyl ether (15.3 mg, 0.16 mmol),

2,6-lutidine (4.0 mg, 0.37 mmol) and deuterium oxide (242.9 mg, 12.1 mmol) in acetone-

d6 (about 1.2 mL). After acquisition of an initial spectrum to set the integral values, 2.10

223

(4.6 mg, 0.0076 mmol, 5 mol %) was transferred quantitatively from a vial using acetone-

d6 in several portions in the J. Young NMR tube. The vial containing 2.10 was washed

with additional acetone-d6 and washings were added to the tube. Total reaction volume

was adjusted to 1.6 mL by addition of acetone-d6. Isomerization and deuteration of the

substrate was monitored at several time intervals with 1H NMR (Table 4.12). Starting

material 1H NMR (500 MHz, acetone-d6) δ 5.84 (tdd, J = 3.2, 12.8, 17.6 Hz, 2H), 5.20

(qd, J = 1.8, 17.2 Hz, 2H), 5.06 (qd, J = 1.4, 10.4 Hz, 2H), 3.90 (td, J = 1.6, 6.2 Hz, 4H).

Product 1H NMR at 48 h (500 MHz, acetone-d6) δ 6.28-6.22 (m, 0.75H), 5.06-4.90 (m,

2H), 1.45-1.52 (m, 0.53H).

Table 4.12. % Hydrogen left at the specified positions of (E)-propenyl ether with deuterium oxide at room temperature

Time (min) 1 2 3

1 76.6 103.1 63.1

2 72.9 102.5 58.1

5 65.7 102.3 46.6

24 47.1 100.7 17.5

48 37.3 100.7 8.9

72 31.4 99.0 7.0

Figure 4.20. Isomerization and deuteration of 4-methyl-1-pentene

Isomerization and deuteration of 4-methyl-1-pentene. A J. Young NMR tube was

charged with tetrakis(trimethylsilyl)methane (a few small crystals), 4-methyl-1-pentene

224

(13.9 mg, 0.165 mmol) and deuterium oxide (142.1 mg, 7.09 mmol) in acetone-d6 (1.0

mL). After acquisition of an initial spectrum to set the integral values, 2.10 (3.7 mg,

0.0061 mmol, 2 mol %) was transferred quantitatively from a vial using acetone-d6 in

several portions into the J. Young NMR tube. Progress of the reaction was monitored via

1H NMR (refer to Table 4.13). Starting material 1H NMR (400 MHz, acetone-d6) δ 5.73

(tdd, J = 7.2, 10.0, 16.8 Hz, 1H), 4.92 (ddt, J = 1.6, 2.0, 14.8 Hz, 1H), 4.87 (ddt, J = 1.2,

2.4, 7.2 Hz, 1H) 1.87 (tt, J = 2.4, 7.2 Hz, 2H), 1.56 (n, J = 6.8 Hz, 1H), 0.82 (d, J = 6.8

Hz, 6H). Product 1H NMR at 24 h (400 MHz, acetone-d6) δ 5.34-5.30 (m, 1.0H), 2.19-2.1

(m, 0.99H), 1.59-1.51 (m, 0.25H), 0.89 (d, J = 6.8 Hz, 6H). 2D NMR at 322 h (400 MHz,

acetone-d6) δ 5.38 (dd, J = 1.0, 2.4 Hz, 1H), 1.52 (d, J = 1.0 Hz, 3H). 13C NMR (400

MHz, acetone-d6) δ 139.5, 139.2, 139.1, 138.9, 121.9, 31.5, 22.8 (m).

Table 4.13. % Hydrogen left at the specified positions of 4-methyl-2-pentene with deuterium oxide at room temperature

Time (min) 1+2 3 4 5

1 73.6 40.0 98.1 101.7

2 68.3 29.0 97.9 100.0

5 61.1 13.9 89.6 97.1

24 50.1 8.6 99.2 102.0

Figure 4.20. Selective deuteration of (+)-limonene

Deuteration of (+)-limonene A J. Young NMR tube was charged with

tetrakis(trimethylsilyl)methane (a few small crystals), (+)-limonene (13.7 mg, 0.10

225

mmol) and deuterium oxide (100.2 mg, 5.0 mmol) in acetone-d6 (about 0.8 mL). After



the J. Young NMR tube was placed in an oil bath at 70 oC. Progress of the reaction was

monitored via 1H NMR (Table 5.14). No isomerization of the double bonds over 144 h at

70 oC was apparent in either this experiment, or a separate control experiment conducted

in the absence of D2O. Starting material 1H NMR (500 MHz, acetone-d6) δ 5.35-5.33 (m,

1H), 4.65-4.64 (m, 2H), 2.03-1.79 (m, 5H), 1.75-1.70 (m, 1H), 1.67 (t, J = 1 Hz, 3H),

1.57 (bs, 3H), 1.44-1.36 (m, 1H). Product 1H NMR at 48 h (500 MHz, acetone-d6) δ 5.37-

5.35 (m, 0.97H), 4.67-4.65 (m, 0.87H), 2.09-1.81 (m, 5H), 1.77-1.72 (m, 1H), 1.69-1.64

(m, 1.30H), 1.59 (bs, 2.83H), 1.46-1.38 (m, 1H).

Table 4.14. % Hydrogen left at the specified positions of (+)-limonene with deuterium oxide at 70 oC

Time (min) 1 2 3 4

0 100.6 98.5 99.1 98.4

1 97.9 97.8 99.6 98.6

2 95.8 94.4 99.1 97.9

5 90.7 90.4 98.4 96.7

24 66.8 66.2 99.4 97.3

48 43.7 43.4 97.1 94.4

120 13.6 13.8 93.3 83.9

226

Figure 4.21. 1H NMR Spectrum of (+)-limonene methyl peak 2

Figure 4.22. Selective deuteration of (+)-valencene

Deuteration of (+)-valencene A J. Young NMR tube was charged with

tetrakis(trimethylsilyl)methane (1.6 mg), (+)-valencene (20.5 mg, 0.10 mmol; sample was

assayed as 88.3% pure by Aldrich) and deuterium oxide (100.6 mg, 5.02 mmol) in

acetone-d6 (about 0.8 mL). After acquisition of an initial spectrum to set the integral

values, 2.10 (3.0 mg, 0.005 mmol, 5 mol %) was transferred quantitatively from a vial

using acetone-d6 in several portions into the J. Young NMR tube. The J. Young NMR

227

tube was placed in an oil bath at 70�C. Progress of the reaction was monitored via 1H

NMR (Table S15). No isomerization of the double bonds over 500 h at 70 oC was

apparent in this experiment. Starting material 1H NMR (400 MHz, acetone-d6) δ 5.27-

5.25 (m, 1H), 4.68-4.62 (m, 2H), 2.31-1.68 (m, 7H), 1.65 (s, 3H), 1.61-1.31 (m, 4H),

1.15-1.02 (m, 1H), 0.90-0.82 (m, 6H). Product 1H NMR at 144 h (400 MHz, acetone-d6)

δ 5.36-5.34 (m, 0.95H), 4.70-4.63 (m, 0.14H), 2.38-1.78 (m, 7.05H), 1.70-1.63 (m,

0.45H), 1.64-1.13 (m, 5.04H), 0.99-0.91 (m, 6.24H). Underlined resonances are those

assigned to exocyclic isopropenyl group.

Table 4.15. % Hydrogen left at the specified positions of (+)-valencene with deuterium oxide at 70 oC

Time (min) 1 2 3

1 101.1 94.5 93.5

24 104.5 49.1 44.1

100 103.3 11.8 19.5

144 95.3 6.9 15.2

Chapter 4 contains material are similar to the material published in the following

papers: Erdogan, Gulin; Grotjahn, Douglas B. “Catalysis of Selective

Hydrogen/Deuterium Exchange at Allylic Positions Using Deuterium Oxide” Topics in

Catalysis 2010, 53, 1055, Erdogan, Gulin; Grotjahn, Douglas B. “Mild and Selective

Deuteration and Isomerization of Alkenes by a Bifunctional Catalyst and Deuterium

Oxide” J. Am. Chem. Soc., 2009, 131, 30, 10354, and Grotjahn, Douglas B; Larsen,

Casey R.; Erdogan, Gulin; Gustafson, Jeffery L.; Nair, Reji; Sharma, Abhinandini

“Bifunctional Catalysis of Alkene Isomerization and Its Applications”, Catalysis of

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Organic Reactions 2009, 123, 379. The dissertation author was the primary researcher for

the data presented.

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(1) Thomas, A. F. Deuterium Labbeling in Organic Chemistry; Appleton-Century-Crofts: New York, New York, 1971. (2) Junk, T.; Catallo, W. J. Chem Soc Rev 1997, 26, 401. (3) Atzrodt, J.; Derdau, V.; Fey, T.; Zimmermann, J. Angew Chem Int Ed Engl 2007, 46, 7744. (4) Garnett, J. L.; Hodges, R. J. J Am Chem Soc 1967, 89, 4546. (5) Klei, S. R.; Golden, J. T.; Tilley, T. D.; Bergman, R. G. J Am Chem Soc 2002, 124, 2092. (6) Golden, J. T.; Andersen, R. A.; Bergman, R. G. J Am Chem Soc 2001, 123, 5837. (7) Klei, S. R.; Tilley, T. D.; Bergman, R. G. Organometallics 2002, 21, 4905. (8) Yung, C. M.; Skaddan, M. B.; Bergman, R. G. J Am Chem Soc 2004, 126, 13033. (9) Skaddan, M. B.; Yung, C. M.; Bergman, R. G. Org Lett 2004, 6, 11. (10) Corberan, R.; Sanau, M.; Peris, E. J Am Chem Soc 2006, 128, 3974. (11) Corberan, R.; Sanau, M.; Peris, E. Organometallics 2006, 25, 4002. (12) Feng, Y.; Jiang, B.; Boyle, P. A.; Ison, E. A. Organometallics 2010, 29, 2857. (13) Ng, S. M.; Lam, W. H.; Mak, C. C.; Tsang, C. W.; Jia, G. C.; Lin, Z. Y.; Lau, C. P. Organometallics 2003, 22, 641. (14) Leung, C. W.; Zheng, W. X.; Wang, D. X.; Ng, S. M.; Yeung, C. H.; Zhou, Z. Y.; Lin, Z. Y.; Lau, C. P. Organometallics 2007, 26, 1924. (15) Lenges, C. P.; Brookhart, M.; Grant, B. E. J Organomet Chem 1997, 528, 199.

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(16) Barthez, J. M.; Filikov, A. V.; Frederiksen, L. B.; Huguet, M. L.; Jones, J. R.; Lu, S. Y. Can J Chem 1998, 76, 726. (17) Lenges, C. P.; White, P. S.; Brookhart, M. J Am Chem Soc 1999, 121, 4385. (18) Rybtchinski, B.; Cohen, R.; Ben-David, Y.; Martin, J. M. L.; Milstein, D. J Am Chem Soc 2003, 125, 11041. (19) Yamamoto, M.; Oshima, K.; Matsubara, S. Heterocycles 2006, 67, 353. (20) Prechtl, M. H. G.; Holscher, M.; Ben-David, Y.; Theyssen, N.; Milstein, D.; Leitner, W. Eur J Inorg Chem 2008, 3493. (21) Meier, S. K.; Young, K. J. H.; Ess, D. H.; Tenn, W. J.; Oxgaard, J.; Goddard, W. A.; Periana, R. A. Organometallics 2009, 28, 5293. (22) Iluc, V. M.; Fedorov, A.; Grubbs, R. H. Organometallics 2011, 31, 39. (23) Rhinehart, J. L.; Manbeck, K. A.; Buzak, S. K.; Lippa, G. M.; Brennessel, W. W.; Goldberg, K. I.; Jones, W. D. Organometallics 2012, 31, 1943. (24) Prechtl, M. H. G.; Holscher, M.; Ben-David, Y.; Theyssen, N.; Loschen, R.; Milstein, D.; Leitner, W. Angew Chem Int Edit 2007, 46, 2269. (25) Werstiuk, N. H.; Chen, J. Can J Chem 1989, 67, 5. (26) Werstiuk, N. H.; Chen, J. Can J Chem 1989, 67, 812. (27) Werstiuk, N. H.; Timmins, G. Can J Chem 1985, 63, 530. (28) Werstiuk, N. H.; Timmins, G. Can J Chem 1988, 66, 2309. (29) Matsubara, S.; Yokota, Y.; Oshima, K. Chem Lett 2004, 33, 294. (30) Ishibashi, K.; Matsubara, S. Chem Lett 2007, 36, 724. (31) Morrill, T. C.; D'Souza, C. A. Organometallics 2003, 22, 1626. (32) Zhou, J. R.; Hartwig, J. F. Angew Chem Int Edit 2008, 47, 5783. (33) Santos, L. L.; Mereiter, K.; Paneque, M.; Slugovc, C.; Carmona, E. New J Chem 2003, 27, 107. (34) Tse, S. K. S.; Xue, P.; Lin, Z.; Jia, G. Adv Synth Catal 2010, 352, 1512.

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CHAPTER 5

CONCLUSIONS AND FUTURE DIRECTIONS

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Applications of imidazolyl phosphines in homogenous and polymer-supported

alkene isomerization and hydrogen-deuterium exchange have been established. Positional

migration of carbon-carbon double bonds can efficiently be achieved with alkene

isomerization catalyst 2.10 with exceptional selectivity for (E)-internal alkenes with

excellent functional group tolerance. Upon immobilization on an insoluble polymer resin,

the selectivity was completely retained with very low metal leaching from the support.

Moreover, 2.10 also proved to be a very efficient catalyst for exchange of allylic protons

of olefins in presence of deuterium oxide. An exceptional degree of deuterium

incorporation was achieved in positions accessible by isomerization in homogenous and

biphasic reaction settings. Further development of 2.10 led to discovery of complexes

that could be capable of controlled mono-isomerization of linear alkenes. Using different

combinations of more hindered phosphines and imidazoles, one can achieve diverse

mixtures of alkenes including polyfunctional examples.

With a bifunctional phosphine library available, one can imagine improving other

organic transformations during which proton transfer or hydrogen bonding could be

important. One of these reactions relevant is palladium-catalyzed coupling reactions that

provide easy access to pharmaceutical ingredients, natural products and many other fine

chemicals. Development and application of highly practical new systems for construction

of C-C and C-X (X = N, O, S) in cross-coupling chemistry have revolutionized the

methods of organic synthesis.1,2 Recently Heck, Negishi and Suzuki have been awarded

the Nobel Prize for their contributions and since the introduction of coupling chemistry in

the early 1970s various industrial processes have been based on this chemistry. For

example, (1) Buchwald-Hartwig amination is used in the Novartis route for synthesis of

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Gleevec3 (Imatinib), (2) Heck coupling is employed in a process for Singulair4-6

developed by Merck and Pfizer’s process for hepatitis C polymerase inhibitor,7 and (3)

Suzuki coupling is employed in synthesis of Losartan8,9 (originally by Merck-Dupont,

now Bristol-Myers Squibb).

Figure 5.1. Pharmaceutical applications of cross-coupling reactions.

The importance of ligand effects on reactivity suggests that ligand electronics and

sterics have profound influence on the oxidative and reductive elimination steps thought

to take place during the catalysis. Palladium coupling reactions of aryl bromides, iodides

and triflates takes place smoothly with widely used triphenyl phosphine, PPh3. Fu et al.10

introduced the use of sterically hindered, electron rich trialkylphosphine ligands (t-Bu3P

and Cy3P) for reactions of aryl chlorides that are more sluggish due to the high bond

dissociation energy of the C-Cl bond, which may be what makes oxidative addition to

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Pd(0) slower.11 Milstein et al. introduced a chelating bisphosphine ligand, 1,3-bis[di-

isopropylphosphino)propane], (dippp), for the carbonylation, formylation, and Heck

reactions of aryl chlorides.12-15 Wide use of several families of ligands has been

implemented: biarylphosphines (Buchwald),16,17 ferrocenylphosphine (e.g. Q-Phos,

Hartwig),18,19 adamantyl phosphines (Beller),20 N-heterocyclic carbenes (Nolan,

Herrmann).21 The importance of bidentate ligands has been long recognized; they can

accelerate the reductive elimination step in the catalytic cycle and reduce the competition

from the beta-hydride elimination side-product formation.22-24 Use of P,N ligands have

recently been employed by Nishikawa,25-27 Andersson,28 and Beller.20,29,30 The family of

P,N bifunctional ligands has great versatility, including possibilities for catalyst tuning as

discussed in Chapter 2.

Figure 5.2. Representative ligands used for cross-coupling reactions

Spectacular successes in improving palladium-catalyzed coupling reactions have

occurred through extensive ligand development. We are investigating the use of

heteroaryl phosphines, which might facilitate stabilization of low coordinate species by

binding to the metal momentarily. Using the imidazolyl ligand library at hand, former

236

group member, Reji Nair, synthesized the following (η3-allyl)palladium chloride

complexes.

Figure 5.3. (η3-Allyl)palladium chloride complexes prepared by Reji Nair

In order to investigate the possible application of these complexes in palladium

catalyzed arylamination reactions, coupling between aryl halide and morpholine (1.5

equivalent) with sodium tert-butoxide (2 equiv) in dimethoxyethane (DME) as solvent

with 5 mol % catalyst 5.1-5.9 was investigated. The reactions were carried out initially at

room temperature, and then heated at 65 oC if no significant progress was observed. The

initial goal was not necessarily to make the best known catalyst for aryl amination, but to

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begin to see what combination of R groups on phosphorus and heterocycle were optimal,

and also see if we could gather evidence for rate acceleration by the heteroaryl group.

Figure 5. 4. Screening reaction and conditions for arylamination

Table 5.1. Results of initial arylamination screening with pre-formed complexes

Yield (%) of 4-(p-tolyl)morpholine Pd-complex

Chlorotoluene Bromotoluene Iodotoluene

5.1 0 15.9 7.7

5.2 0.5 40.2 27.1

5.3 0.4 27.0 19.8

5.4 0 11.7 3.9

5.5 0.2 62.7 39.1

5.6 0.5 18.3 18.5

5.7 0 2.6 1.9

5.8 0.5 9.2 NA

5.9 1.0 17.3 8.3

Screening with these pre-formed complexes showed that several complexes are

capable of product formation with 4-iodo- and 4-bromotoluene under the conditions

tested. With results from these initial screenings, testing of catalysts generated more

conveniently in situ is being investigated to determine the practicality of these ligands

along with control ligands to determine the effect of imidazolyl phosphines. Another

study is to be conducted on the effect of palladium source used; a recent review31

suggests that the crotylpalldium complexes are superior to allylpalldium complexes in

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amination of 4-bromoanisole with N-methylaniline32 and Suzuki coupling of 4-

bromoanisole with p-(tert-butyl)phenyl)boronic acid.31

Figure 5.5. In situ arylamination screening ligands and palladium precursors

239

These studies in part are being currently investigated and prepared for future

submission for publication by Reji Nair, Gulin Erdogan, Christoffel van Niekerk, Alice

Lu, James Golen, Antonio DiPasquale, Arnold Rheingold, and Douglas Grotjahn.

In summary, use of P, N ligands that have a pendant nitrogen (imidazole,

pyridine) which can act as proton or hydrogen bond acceptor has led to dramatic

improvement in a variety of reactions. In the case of anti-Markovnikov alkyne hydration,

the change in rate introduced by 1.6 (Chapter 1) was greater than 2.4 x 1011 and the

change in selectivity was 300,000 that can be compared to enzyme-like enhancements.

Here in this thesis, alkene isomerization catalyst 2.10 (Chapter 2), improves TOF as

much as 10,000 times compared to a system that lacks the nitrogen bifunctionality. Now,

the two bifunctional catalysts mentioned are both sold commercially, showing broad

impact of the research.

All of these observations suggest that use of P, N ligands with pendant bases can

be useful tools in reactions that involve proton movements, other than the reactions

discussed here, such as alkene or diene functionalization with protic reactants like

alcohols or amines, and C-H activations or functionalizations, all possibilities for future

investigation.


material. Nair, Reji; Erdogan, Gulin; van Niekerk, Christoffel, Golen, James; Rheingold,

Arnold; Grotjahn, Douglas. The dissertation author was the primary researcher for the

data presented.

240

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Metal complexes with bifunctional imidazolyl phosphines for catalytic organic transformations

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